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By Tsegay. H.
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Physiology of cell and cell signalling
by Tsegay. H.
What is cell?
Cells are the smallest structural and functional unit of all living things,
Our body is an aggregate of 100 trillions of different cells all working together for the maintenance of the entire organism.
A typical cell has two parts: nucleus and cytoplasm. The cytoplasm is separated from the surrounding fluid (ECF) by
the plasma membrane. The nucleus is separated from the cytoplasm by a nuclear
membrane
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Structural levels of organization of human bodyMuscle cells
Nerve cells Cells: 4 types Epithelial cells
Cells in the connective tissues Muscle tissue
Tissues 4 types Nerve tissue Epithelial tissue connective tissues
Organs: Example: Heart, lungs that are made up of 4 types of tissues
Organ system: Example: Respiratory system, CVS
Organism: Human organism
Cells of different tissues and organs vary in structures and functions; However, there are certain characteristics
common to all cells: Growth and development, Irritability, Movement, Reproduction, Excretion
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Parts of the Cell Typical cell has two parts: nucleus and cytoplasm.
The nucleus is separated from the cytoplasm by a nuclear membrane and the cytoplasm is separated from the surrounding fluid (ECF) by the plasma membrane.
Cytoplasm The gel-like material within the cell membrane It is a fluid matrix composed of water, salts, organic
molecules and many enzymes that catalyze reactions, along with dissolved substances such as proteins and nutrients.
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Functions of cytoplasm
Helping to maintain the shape and consistency of the cell
Providing suspension to organelles The very specialized structures suspended in the
cytoplasm are organellesAs site of storage for chemical substances
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The nucleus The nucleus is the control center for the cells. It contains the genes, which are hereditary units Chemically each gene consists of highly compressed DNA in the
form of chromosomes Genes control cellular activity by determining the type of
proteins, enzymes, and other substances that are made by the cell.
The nucleus is also the site of RNA synthesis There are three kinds of RNA:
Messenger RNA (mRNA), which carries the instruction from DNA for protein synthesis to the cytoplasm
Ribosomal RNA (rRNA), which moves to the cytoplasm where it becomes the site of protein synthesis
Transfer RNA (tRNA), serves as an amino acid transporter system within the cell for protein synthesis.
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DNA and RNA are made up of nucleotidesNucleotides are composed of nitrogen containing bases
purine (A, G) and pyrimidin (C, T) as well as deoxyribose sugar conjugated by phosphate.
In RNA, the pyrimidin base T is replaced by U and the 5-carbon sugar is ribose.
In addition to the chromatin, the nucleus contains one or two round bodies called nucleoli.
It is here that rRNA is synthesized. The nuclear contents are surrounded by a double walled
nuclear membrane. The pores present in this membrane allow fluids, electrolytes,
RNA, and other materials to move between the nuclear and cytoplasmic comportments.
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Functions of nucleotides1.Building units of nucleic acid (DNA, RNA)2.High energy molecules (ATP, GTP)3.Biosynthetic mediators (UDP-glycogen) 4.Regulator of chemical reaction in the cell e.g. cAMP5.Act as coenzyme (NAD, FAD)
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Cellular organelles Are ‘specialized structures suspended in the cytoplasm’ These include the ribosome, endoplasmic reticulum (ER)
Golgi apparatus, mitochondria, lysosomes, and the cytoskeletal system (microtabules and microfilaments).
Ribosomes Are the sites of protein synthesis in the cell Small particles composed of rRNA and proteins Found in two forms: attached to the wall of ER or as free
ribosomes. Free ribosomes are found in two forms
Scattered in the cytoplasm and Clustered (aggregated) to form functional units called
polyribosomes
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Endoplasmic reticulum (ER) It is an extensive membranous structure that connects
various parts of the inner cell. ER is also connected with the nuclear membrane.
There are two types of ER: rough ER and smooth ER. The rER is studded with ribosomes.
The function of rER is to segregate proteins that are being exported from the cell.
orER =protein synthesis.
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Endoplasmic reticulum (ER) cont……d The sER is free of ribosome. Function of sER varies in
different cells. The sarcoplasmic reticulum of
skeletal and cardiac muscle cells are forms of sER. Calcium ions needed for
muscle contraction are stored and released from the sarcoplasmic reticulum of muscle cells.
In the liver, the sER is involved in glycogen storage and drug metabolism. o sER can synthesize a group
of drug metabolizing enzymes called microsomal system.
Endoplasmic reticulum (rER and sER)
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Golgi Complex= delivery center of the cells
The Golgi complex consists of flattened membranous saccules and cisterns that communicate with the ER and acts as a receptacle for hormones and others substances that the ER produces.
It then modifies and packages these substances into secretary granules.
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MitochondriaThe mitochondria are literally the “power plants” of the cell,
capable of producing the energy rich compound ATP, which is required for various cellular activities.
The mitochondria require oxygen to produce energy (ATP) from food stuffs.
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Mitochondria
Lysosomes Lysosomes are sac-like compartments that contain a
number of powerful digestive enzymes. They break down harmful cell products and waste
materials, cellular debris, and foreign invaders such as bacteria, and then force them out of the cell.
Degrade old dead cells and phagocytosis of microrganisms
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Cytoskeletal system of the cell Composed of microfilament and microtubules Rigid threadlike structures dispersed through out the
cytoplasm Function of cytoskeletal system:
1. Maintain shape of the cells. 2. Serve as a transport system for the movement of
compounds and organelles within the cell. 3. Provide for the support and movement of cilia and flagella4. Cell to cell contact: to fasten cell membranes together
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The plasma membrane It is a sheet-like structure that surround (enclose) the cell,
separating the cellular contents from the ECF. It is entirely composed of proteins and lipids in a ratio of
55:43 respectively, and 3% of carbohydrates. Percent proportion
Proteins: 55 %
Phospholipids 25 % Lipids: 42 % Cholesterol 13 %
Neutral fats 4 % Carbohydrate: 3 %
The level of cholesterol determines rigidity of the membrane
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Function of the plasma membrane Separates cellular contents from the ECF Regulates the passage of substances in and out.
It is semi-permeable allowing some subs to pass through it excluding others. oThis creates unequal distribution of ions on both sides
of the membrane. It provides receptors for NTs, hormones and drugs. It is a means of cell to cell contact. Plays an important role in the generation and transmission of
electrical impulse in nerves muscle. Involved in the regulation of cell growth and proliferation.
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Structure of the cell membrane A plasma membrane is a fluid in its nature, The cell membrane consists of an organized arrangement of
proteins, lipids and CHOs 1. Lipids: The major lipids are phospholipids such as phosphatidyl
choline and phosphatidyl-ethanolamine, and cholesterol. Lipids form the basic structure of the membrane. The lipid molecules are arranged in two parallel raws, forming a
lipid bilayer.
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Structure of the cell membrane cont….d The phospholipids component is organized into a double layer with their
hydrophobic (tail) directed towards the center of the membrane and polar hydrophilic heads directed out ward facing ECF and ICF.
The lipid bilayer portion of the cell membrane is impermeable to water and water soluble substances such as ions, glucose, urea and others.
On the other hand, fat soluble substances such as O2, CO2, alcohol and drugs can penetrate this portion of the membrane.
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Structure of the cell membrane cont….d
2. Proteins: are two types
A. Integral or intrinsic proteins: Interdingitated in the hydrophobic center of the lipid
bilayer Transmembrane proteins are integral proteins that
span the entire bilayer. Transmembrane proteins serve as:
Channels through which ions pass Carriers which actively transports material. across
the bilayer e.g. glucose Pumps which actively transport ions Receptors for neurotransmitters and hormones
Integral proteins that are present only on one side of the membrane, serve primarily as enzymes.
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B. Peripheral or extrinsic proteins: Bind to the hydrophilic polar heads of the lipid or on integral proteins. Peripheral proteins that bind to the intracellular surface contribute
to the cytoskeleton. Peripheral proteins that bind to the external surface contribute to the
glyco-colgx, a cell coat that is composed of glycol-lipids and glycol-proteins to cover the cell membrane
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3. Carbohydrates Attached invariably on the outside surface of the
membrane, binding with protruded integral proteins and lipid, they form glyco-proteins and glyco-lipid (glycocalyx) respectively.
They play a role in
1. Immune reaction (antigenical importance),
2. Cell to cell attachment and
3. Act as receptors for NTs, hormones and drugs
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Transport through the cell membrane Substances are
transported through the cell membrane by:
1. Simple diffusion2. Osmosis3. Facilitated diffusion4. Active transport (1O
and 2O) and 5. Vesicular transport
mechanisms.
ECF
ICF
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1. Simple Diffusion Diffusion is passive movement of substances down their
concentration gradient. Factors affecting the net rate of diffusion
Lipid solubility of the substancesMembrane permeability Concentration difference or Pressure differenceElectrical potential difference of ions
Membrane permeability is affected byMembrane ThicknessLipid solubilityNo of ion channels per unit areaTemperature: T = thermal motion of molecule
permeabilityMW
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Simple Diffusion cont….d Rate of diffusion is determined by the following factors
summarized in the formula shown below. S. A. T. C
Rate of diffusion = D. MW
Where, C = Change of concentrationS = Solubility in lipidA = Surface area of the membraneT = TemperatureD = Distance or membrane thicknessMW = Molecular wt of substances
Examples: Substances that are transported by simple diffusion are CO2, O2, alcohol, lipid soluble drugs and ions through specific channels.
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2. Osmosis It is the power of movement of H2O
from an area of higher amount of water to an area of lower amount of water through the semi permeable membrane.
The direction of movement of water is governed by the amount of osmoticaly active particles (solutes).
The pressure that opposes osmosis of water is called osmotic pressure
H2O molecules have very small (0.3 nm) in diameter, so that they can not traverse the lipid bilayer simply. Instead they pass through specific water channels called aquaporins:
Five aquapurins (AQ1….AQ5) have been identified in the body.
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3. Facilitated diffusionCarrier mediated transportCarriers are saturable, do
not need energyTransports substances
down their concentration gradient
Examples: transport of glucose, proteins. (Macromolecules)
Glucose
Carrier protein
Cell membraneECF
ICF
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4. Active transport Substances are transported
against concentration, electrochemical gradient, up hill direction.
Used for the transport of Na+, K+, Ca2+, Fe2+, H+, Cl-
Consumes energy in the form of ATP
Primary active transport Carrier protein are involvedConsumes energy from
ATPCarrier protein is anti-
porter
Common examples1. Na+ - K+ ATPase2. H+ - K+ ATPase3. Ca2+ ATPase
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Secondary active transport Carrier protein are involved Energy is not from ATP, but
from other ions Carrier protein is symporter
Uniport carriers: Carry single substance to one directionAntiport carriers: Carry two substances in opposite directionsSymport carriers: Carry two substances into the same direction
5. Visicular transport Vesicles or other bodies in the cytoplasm move macromolecules
or large particles across the plasma membrane. Types of vesicular transport include:
Exocytosis: vesicles fuse with the plasma membrane, then releasing their contents to the outside of the cell.
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Endocytosis: capturing of a substance outside the cell, then the plasma membrane merges to engulf it. The substance subsequently enters the cytoplasm enclosed
in a vesicle. There are two kinds of endocytosis:
Phagocytosis or cellular eating occurs when the dissolved materials enter the cell.
Pinocytosis or cellular drinking occurs when the plasma membrane folds inward to form a channel allowing dissolved substances to enter the cell.
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Intercellular communication The intercellular signaling is subdivided into the following
classifications: Neurotransmitters are released by axon terminals of neurons
into the synaptic junctions and act locally to control nerve cell functions.
Endocrine hormones are released by glands or specialized cells into the circulating blood and influence the function of cells at another location in the body.
Neuroendocrine hormones are secreted by neurons into the circulating blood and influence the function of cells at another location in the body.
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Paracrines are secreted by cells into the ECF and affect neighboring cells of a different type.
Autocrines are secreted by cells into the extracellular fluid and affect the function of the same cells that produced them by binding to cell surface receptors.
Cytokines are peptides secreted by cells into the extracellular fluid and can function as autocrines, paracrines, or endocrine hormones. Examples interleukins that are secreted by helper T cells
act on other cells of the immune system Cytokine hormones (e.g., leptin) produced by
adipocytes are sometimes called adipokines.
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Cell junctions
The points of contact between two adjacent plasma membranes, cell junctions.
There are 3- types of cell junction:Tight junctionsAnchoring junctionsCommunicating junctions
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Tight junctions
Cells are attached tightly with belt like structure so prevent fluid to pass between
Are common among epithelial cells of the stomach, intestine, and urinary bladder.
They prevent the fluid in a cavity from leaking into the body by passing between cells.
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Anchoring junctions
Are common in tissues subjected to traction and stretching such as the outer layer of the skin, cardiac muscle, and uterus.
Anchoring junctions include desmosomes, hemidesmosomes and adherence junction.
Adherence junctions connect to microfilaments of the cytoskeleton and link cells to one another or anchor cells to extracellular materials.
Desmosomes form a firm attachment between cells some what like spotwelds.
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Communicating junctions (Gap junctions) Are narrow channels that directly connect the cytoplasm of
two neighboring cells, consisting of proteins called connexons.
These proteins allow only the passage of ions and small molecules. oGap junctions allow communication between cells
through the exchange of materials or the transmission of electrical impulses.
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Cell junctions
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What tissue mean?
Cells of similar function, come together and form higher level of body’s organization, tissue. Cooperative unit of very similar cells that
perform a specific function. There are four main types of tissues:
oNervous tissueoMuscle tissueoConnective tissueoEpithelial tissue
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1.Epithelial Tissue
Cells are tightly fitted together in continuous layers, Tight packaging allows tissue to act as a
barrier to protect against mechanical injury, infection, and fluid loss,
Cover outside of body (skin) and line organs and internal body cavities (mucous membranes of digestive, respiratory, and reproductive systems).
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Epithelial Tissue Covers and Lines the Body and its Parts
A. Simple squamous(Lung air sacs)
D. Statified squamous(Lining esophagus)
B. Simple cuboidal(Kidney tubes)
C. Statified columnar(Lining intestine)
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Epithelial tissues, mucous membranes, absorb and secrete chemical solutions.Mucous membranes:
–Digestive tract epithelium (mucous membranes) secretes mucus and digestive enzymes.
–Respiratory tract epithelium secretes mucous that helps trap dust particles before they reach the lungs.
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2. Connective Tissue
Connective tissues are fibrous tissues Are made up of cells separated by non-living material,
which is called extracellular matrix. Functions:
As the name implies, connective tissue serves a "connecting" function.
It supports and binds other tissues.Gives shape to organs and holds them in place.
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Types of connective tissue
A. Loose connective tissue Most widespread connective tissue Loose matrix with fibers, packing material Function: Attaches skin to muscles, binds
and holds tissues and organs in place
B. Adipose (fat) tissue Protection Insulation Energy storage
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Types of connective tissue cont…..d
C. Blood
The only fluid connective tissue
Composed of plasma having water, plasma proteins, and other substances, and Cellular elements [RBCs, WBCs and platelets]
Function:
Transporting function
Regulatory function [water, temperature, pH…..]
Protective function [stoppage of bleeding, engulfing invaders, development of body immunity]
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Types of connective tissue cont…..d
D. Fibrous Connective Tissue
Matrix of closely packed collagen fibers,
Strong and non-elastic,
Found in:
Tendons: Attach muscles to bones
Ligaments: Attach bone to bone
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Types of connective tissue cont…..d
E. Cartilage
Hard matrix with collagen fibers
Found on end of bones, nose, ears, and between vertebra.
F. Bone
Supports the body
Solid matrix of collagen fibers and calcium, phosphate, and magnesium salts.
Bone is harder than cartilage, but not brittle because of collagen.
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Connective Tissue Binds and Provides Support
A. Loose Connective Tissue
B. Adipose Tissue
C. Blood
D. Fibrous Connective Tissue
E. Cartilage
F. Bone 52
3. Muscle TissueMuscle, the most abundant type of tissue, is the fleshy
organ of the body that converts potential energy of food into mechanical energy [produce force and movement] to perform different activities.
Made up of long cells [sacromers = contractile unit of muscle] that contract when stimulated by nerve impulses.
Muscle cells have many microfilaments made up of actin and myosin.
Muscle contraction accounts for much of energy consuming work.
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There are three types of muscle tissue
A. Skeletal (striated) muscle
Located attached to bones by tendons & moves skeleton
They are elongated, cylindrical, multinucleated cells, and striated
Innervated by somatic nerve system
Responsible for voluntary movements.
B. Cardiac muscle Striated, uni or bi nucleated muscles found in
walls of the heart forming contractile tissue of heart.
Controlled by autonomic nerve system, drugs and hormones [are involuntary muscles]
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C. Smooth muscle Found in walls of visceral organs [digestive tract, bladder,
arteries, uterus, and…….]
Non-striated and mono-nucleated cells
Responsible movement of different activities with in the body.
[food, dust particles, child during delivery, urine, sperm,
ovum……]
Contract more slowly than skeletal muscle, but can remain
contracted longer.
Controlled by autonomic nerve system, drugs and hormones [are
involuntary muscles].
Both cardiac and smooth muscles have authorythamic property,
[generate action potential even with out nerve supply] 55
A. Skeletal muscle
B. Cardiac muscle
C. Smooth muscle
Types of Muscle
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4. Nervous Tissue Senses stimuli[receptors], carry sensory information
[sensory =afferent pathway] to CNS where it is processed and appropriate information is formulated [association neurons], then transmit the formulated response[motor =efferent pathway] to the glands and muscles[ effector organs]Controls the activity of muscles and glands, and
allows the us to respond to its environment.
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Types of nervous tissueNervous tissue made up of two types of cells:
Neuron Structural and functional unit of nervous tissue. Consists of:
Cell body: Contains cell’s nucleus.Dendrite: Extension that conveys signals
towards the cell body. Axon: Extension that transmits signals away
from the cell body. Supporting cells(neuroglial cells)
Nourish, protect, and insulate neurons.58
Nervous Tissue Forms a Communication Network
Excitable Tissues? The term excitability refers to an ability of a tissues
to receive stimuli and respond to that stimuli. Excitable tissues respond to various stimuli by
rapidly changing their resting membrane potentials and generating electrochemical impulses (action potential).
The stimuli can be electrical, chemical, mechanical or thermal.
There are two types of excitable tissues:Nerve Muscle
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1. Nervous System Organization of the Nervous System
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Nervous System1. Central Nervous System (CNS)
Spinal cord and brain Function: integrate, process and coordinate sensory input
and motor output2. Peripheral Nervous System (PNS)
All neural tissue outside CNS Function: carry information to and from CNS Composed of:
Cranial nerves (12 pairs) to and from brainSpinal nerves (31 pairs) to and from spinal cord
Nerve = bundle of axons (nerve fibers) with blood vessels and connective tissues.
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Divisions of PNS1. Sensory/Afferent Division
Carry sensory information to CNSGrouped in to:
I. Somatic afferent division Carry sensory information of voluntary activities like
of skin, skeletal muscles, joints
II.Visceral afferent divisiono Carry sensory information of involuntary activities
like glands and smooth muscles of internal organs
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2. Motor/Efferent Divisiono Carry information from CNS to effectors o Grouped to:
A. Somatic Nervous SystemVoluntary nervous system Carry to skeletal muscles
B. Autonomic Nervous System (ANS) Involuntary nervous systemCarry to smooth & cardiac muscle, glandsCould be:
Sympathetic Division: “fight or flight”Parasympathetic Division: “rest and digest”
They antagonize each other
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Nerve tissueTwo principal cell types that make up the nerve system are neurons and neuroglial cells
Neurons are ‘functional units of the nerve system’ o Neurons are specialized for the generation and transmission
of nerve impulse.Sensory functionGeneration of thoughtStorage of memoryIntegration of ideaCoordination of muscular activities
Neuroglial cells:o The neuroglial cells are non excitable cells found in
association with neurons. o They provide supporting functions to the neuron.
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Neuroglial cells outnumber neurons by about 20x
5 types of supporting cells, 4 are found in the CNS:
1. Astrocytes Star-shaped, abundant, and
versatile cells Guide the migration of
developing neurons Involved in the formation of
the blood brain barrier Function in nutrient
transfer Interconnect blood vessels
and nerve fibers.
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Neuroglial cells cont….d
2. Microglial cells Specialized immune cells that
act as the macrophages of the CNS
3. Ependymal Cells Line the ventricles of the
brain and the central canal of the spinal cord
Some are ciliated which facilitates the movement of cerebrospinal fluid
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4. Oligo-dendrocytes Produce the myelin
sheath which provides the electrical insulation for neurons in the CNS
5. Schwann cells Form myelin sheaths
around the larger nerve fibers in the PNS.
Vital for neuronal regeneration
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Neurons: Functional structures Neurons are functional units of the
nervous system. Specialized to conduct information from
one part of the body to another A typical neuron has three distinct parts.
These are: Dendrites, Cell body & Axon.Dendrites: Collect information and
send it to cell body. Cell body: Connect dendrites and
axon, main bio-synthetic and metabolic center
Axon: Take information away of cell body to another cell
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Neurons: morphological classification
Structurally neurons are classified into three classes:
1. Multipolar neurons(neurons having more than 2 processes) found in the CNS, motor in function
2. Bipolar neurons (neurons with 2 processes): found in the retina and inner ear
3. Unipolar neurons (neurons having only one process): sensory in function
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Functional Classification of Neurons Functionally, there are thee classes of neurons:
1. Sensory(afferent) neurons: conduct impulses from periphery to the central nerve system
2. Inter-neurons (association or integrative) neuron:o Receive and interpret sensory information o Conduct formulated response to effectors via motor
area.3. Motor (efferent) neurons: conduct impulses from
central nerve system (brain & spinal cord) to the periphery
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Myelin?
Is electrically insulating material that forms a layer, the myelin sheath, usually around only the axon of a neuron.
Myelin is an outgrowth of glial cell. The production of the myelin sheath is called
myelination It is essential for the proper functioning of the nervous
system. In humans, the production of myelin begins in the 14th
week of fetal development, although little myelin exists in the brain at the time of birth.
Myelin cont….d
• During infancy, myelination occurs quickly and continues through the adolescent stage of life.
• Schwann cells supply the myelin for peripheral neurons, whereas oligodendrocytes, myelinate the axons of the central nervous system.
Composition of myelin
• Myelin may be made by different cell types, varies in chemical composition and configuration, but performs the same insulating function.
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Composition of myelin cont…..d Myelin is about 40 % water;
The remaining dry mass of myelin is about 70 - 85 % lipids and about 15 - 30 % proteins.
Some of the proteins that make up myelin are Myelin basic protein (MBP), Myelin oligodendrocyte glycoprotein (MOG), and Proteolipid protein (PLP).
The primary lipid of myelin is a glycolipid called galactocerebroside (GalC).
The intertwining hydrocarbon chains of sphingomyelin serve to strengthen the myelin sheath.
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Myelination in the CNS Myelination in the PNS
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Myelin cont….d
The wrapping is never complete Interspersed along the axon are gaps where there is no myelin – these are nodes of Ranvier.
Function of myelin sheathProtects axonFacilitate rate of action potential conductionSaves ATP
The soma Is where the signals from the dendrites are joined and passed on The soma and the nucleus and organelles do not play an active
role in the transmission of the neural signals. Instead, serve to maintain the cell and keep the neurons
functional. The supporting structures of the cell include mitochondria,
which provide energy for the cell, and the Golgi apparatus, which packages products created by the cell and secretes them
outside the cell wall.
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Soma cont….d Contains nucleus and normal organelles
Biosynthetic center of the neuron Contains a very active and developed rough endoplasmic
reticulum which is responsible for the synthesis of NTs. The neuronal rough ER is referred to as the Nissl body.
Contains many bundles of protein filaments (neurofibrils) maintain the shape, structure, and integrity of the cell.
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Soma cont….d Clusters of soma in the CNS are known as nuclei Clusters of soma in the PNS are known as ganglia
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Nerve fiber Is a threadlike extension of a nerve cell A nerve fiber may be myelinated and/or
unmyelinated.
Found both in the central and peripheral nervous system.
Consists of an axon and myelin sheath (if present) in the nervous system.
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Nerve fiber cont…….d In the central nervous system (CNS), myelin is produced
by oligodendroglia cells. Schwann cells form myelin sheath in the peripheral
nervous system (PNS). Schwann cells can also make a thin covering for an
axon which does not consist of myelin (in the PNS)= endoneurium
A peripheral nerve fiber consists of an axon, myelin sheath, Schwann cells and its endoneurium.
There are no endoneurium and Schwann cells in the central nervous system.
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Classification of nerve fibers
1. Central nerve fibers In CNS, nerve fibers differ in terms of size, conduction
velocity, and presence or absence of myelin. For example, the olfactory nerve fibers are short and
unmyelinated, but the optic nerve fibers are myelinated A bundle of nerve fibers in CNS constitutes = tract
The pyramidal tract and extra pyramidal tracts have long nerve fibers that descend from the brain to the spinal cord.
These fibers have an important role in motor control, and are known as descending tracts.
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There are other bundles of nerve fibers in the CNS are called ascending tracts.These carry sensory information from the periphery to
the different areas of the brain.
Peripheral nerve fiber types A nerve may be sensory, motor or sensory-motor (mixed). There are three types of nerve fibers in a mixed nerve:
Sensory nerve fibers (afferent fibers)Motor nerve fibers (efferent fibers)
Autonomic nerve fibersSomatic nerve fibers
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Components of peripheral nerve fiberEach peripheral nerve fiber contains:
An axonAxolemmaMyelin sheath (if present)Schwann's sheath (neurolemma)Endoneurium, [endoneurial channel, sheath or tube], is
a layer of weak connective tissue made up of endoneurial cells that encloses the myelin sheath of peripheral nerve fiber.
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Classification of peripheral nerve fibers There are three types of peripheral nerve fibers based on
their diameter and myelination:A groupB groupC group
A groupHave a large diameter and are myelinated fibers, high
conduction velocity, and.The A group consists of four types of nerve fibers:
A alpha fibers (afferent or efferent fibers) A beta fibers (afferent or efferent fibers) A gamma fibers (efferent fibers)A delta fibers (afferent fibers)
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Motor fibers of the A group
A alpha fibersHigh conduction velocity.Alpha motor neurons innervate extrafusal muscle fibers
A beta fibersBeta motor neurons innervate intrafusal muscle fibers of
muscle spindles (nuclear bag and nuclear chain fibers), with collaterals to extrafusal muscle fibers.
A gamma fibersGamma motor neurons innervate intrafusal muscle fibers
of muscle spindles (nuclear bag and nuclear chain fibers).
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Sensory fibers of the A group
A alpha fibers (Ia fiber or Ib fibers) Characteristics:
High conduction velocity Ia fibers are related to muscle spindle primary endings
(muscle sense) Ib fibers are related to golgi tendon organs (muscle sense)
A beta fibers (II fibers) II fibers carry sensory information related to muscle spindle
secondary endings, touch, and kinesthesia.
A delta fibers (III fibers) III fibers carry sensory information related to pain,
temperature, crude touch, and pressure.
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B group Are myelinated with a small diameter They are the preganglionic fibers of the autonomic nervous
system. Have low conduction velocity.
C group Are unmyelinated and as the B group fibers have a small
diameter and low conduction velocity. These fibers include:
Postganglionic fibers in the autonomic nervous system (ANS)
Nerve fibers at the dorsal roots These fibers carry the following sensory information:
pain, temperature, touch, pressure and itch
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Neuronal Processes• Axons: myelinated/unmylinated• Most neurons have a single axon – a
long (up to 1m) process designed to convey information away from the cell body.
• Originates from a special region of the cell body called the axon hillock.
• Transmit APs from the soma toward the end of the axon where they cause NT release.
• Often branch sparsely, forming collaterals.
• Each collateral may split into telodendria which end in a synaptic knob, which contains synaptic vesicles – membranous bags of NTs.
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Classification of Ion Channels
I. Leak channel
II. Gated Channel Na+ channels There are three major types;
Na+ leak channels Voltage-gated Na+ channels Ligand (chemical –gated) Na+ channels
K+ Channels There are four major classes:
K+- leak channelsVoltage-gated K+ channelsLigand- gated K+ channelsG-prorein- gated K+ channels
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Ca+ Cahnnels Are the following:Voltage- gated Ca+ channels with subtypes
L-type Ca+- gated channelsT- type Ca+- gated channelsN-type Ca+- gated channels
Ligand- gated Ca+- gated channelsG- protein-gated Ca+- gated channels
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The Na+-K+ channel causes large concentration gradients for sodium and potassium across the resting nerve membrane.
These gradients are the following:Na+ outside =142mEq/L, Na+ inside =14mEq.LK+ outside = 4mEq/L, K+ inside = 140mEq/LThe ratios of these two respective ions from the inside to
the outside areNa+ inside/Na+ outside =0.1
K+ inside/K+ outside =35
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All cells have a voltage difference across their plasma membrane.
This is called membrane potential.
The membrane potential (VM) at rest is called resting membrane potential (RMP)
The RMP of a typical neuron is -90 mv Meaning, ‘at rest there is more electro-positivity out and
electro-negativity inside the cell membrane of the neuron.’
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Origin of Resting Membrane Potential
1. Leakage of Potassium and Sodium through the Nerve MembraneThe nerve membrane contains channel protein through
which potassium and sodium ions can leak, called a potassium-sodium (K+-Na+) "leak" channel. oOn average, the channels are far more permeable to
potassium than to sodium, normally about 100 times as permeable and hence K+ plays a major role than Na+.
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2. Contribution of the Potassium Diffusion Potential The diffusion potential level across a membrane that exactly
opposes the net diffusion of a particular ion through the membrane is called the Nernst potential for that ion.The magnitude of Nernst potential is determined by the
ratio of the concentration of specific ion on the two sides of the membrane.
The greater this ratio, the greater the tendency for the ion to diffuse in one direction, and therefore the greater the Nernst potential required to prevent additional net diffusion.
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• The following equation, called the Nernst equation, can be used to calculate the Nernst potential for ion at normal body temperature of 37°C:
• EMF (in mv) is electromotive force
EMF=+ 61 log concentration inside
concentration out side
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When using this formula, it is usually assumed that the potential in the extracellular fluid, outside the membrane remains at zero potential, and the Nernst potential is the potential inside the membrane. Thus, when the concentration of positive potassium ions on the inside is 10 times that of the outside, the log of 10 is 1, so that the Nernst potential calculates to be -61 millivolts inside the membrane
We make the assumption that the only movement of ions through the membrane is diffusion of potassium ions between inside and outside the membrane.
Because of the high ratio of potassium ions inside to outside, 35:1, the Nernst potential = the logarithm of 35 is 1.54, and times -61 millivolts is -94 millivolts.
Therefore, if potassium ions were the only factor causing the resting potential, the resting potential inside the fiber would be equal to -94 millivolts.
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3. Contribution of Sodium Diffusion through the Nerve Membrane.
There is slight permeability of the nerve membrane to sodium ions caused by the minute diffusion of sodium ions through the K+-Na+ leak channels.
The ratio of sodium ions from inside to outside the membrane is 0.1, and this gives a calculated Nernst potential for the inside of the membrane of +61 millivolts.
But the Nernst potential for potassium diffusion is -94 millivolts.
How do these interact with each other, and what will be the summated potential?
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Calculation of the Diffusion Potential When the Membrane Is Permeable to Several Different Ions
• When a membrane is permeable to several different ions, the diffusion potential that develops depends on three factors: (1) the polarity of the electrical charge of each ion, (2) the permeability of the membrane (P) to each ion, and (3) the concentrations (C) of the respective ions on the inside (i) and outside (o) of the membrane.
• Thus, the following formula, called the Goldman equation, or the Goldman-Hodgkin-Katz equation, gives the calculated membrane potential on the inside of the membrane when two univalent positive ions, sodium (Na+) and potassium (K+), and one univalent negative ion, chloride (Cl-), are involved.
EMF=-61 log C Na+i P Na+ + C K+
i P K+
C Na+o P Na+ + C K+
o P K +
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• This can be answered by using the Goldman equation described previously.
• Intuitively, one can see that if the membrane is highly permeable to potassium but only slightly permeable to sodium, it is logical that the diffusion of potassium contributes far more to the membrane potential than does the diffusion of sodium.
• In the normal nerve fiber, the permeability of the membrane to potassium is about 100 times as great as its permeability to sodium.
• Using this value in the Goldman equation gives a potential inside the membrane of -86 millivolts, which is near the potassium potential
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4. Contribution of the Na+-K+ Pump. The Na+-K+ pump provides an additional contribution to the
resting potential. There is continuous pumping of three sodium ions to the
outside for each two potassium ions pumped to the inside of the membrane by hydrolyzing one ATP
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This creates an additional degree of negativity (about -4 millivolts additional) on the inside beyond that which can be accounted for by diffusion alone.
There are also negatively charged non-diffusible proteins within the ICF that cannot travel through the membrane.What this adds up to is the fact that the inside of the cell is
negative with respect to the outside. The interior has less positive charge than the exterior.
Therefore, the net membrane potential with all these factors operative at the same time is about -90 millivolts.
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In summary,
• The diffusion potentials alone caused by potassium and sodium diffusion would give a membrane potential of about -86 millivolts, almost all of this being determined by potassium diffusion.
• Then, an additional -4 millivolts is contributed to the membrane potential by the continuously acting electrogenic Na+-K+ pump, giving a net membrane potential of -90 millivolts.
• There are also negatively charged non-diffusible proteins within the ICF that cannot travel through the membrane
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Nerve Action Potential
• Nerve action potentials are rapid changes in the resting membrane potential that spread rapidly along the nerve fiber membrane.
• Each action potential begins with a sudden change from the normal resting negative membrane potential to a positive potential and then ends with an almost equally rapid change back to the negative potential.
• To conduct a nerve signal, the action potential moves along the nerve fiber until it comes to the fiber's end.
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The successive stages of the action potential are as follows:
1. Resting Stage: This is the resting membrane potential before the action
potential begins. The membrane is said to be "polarized" during this stage
because of the -90 mv negative membrane potential that is present.
To explain more fully the factors that cause both depolarization and repolarization, we need to describe the special characteristics of two other types of transport channels through the nerve membrane: the voltage-gated sodium and potassium channels.
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2. Depolarization Stage: At this time, the membrane suddenly becomes very permeable
to sodium ions, allowing tremendous numbers of positively charged sodium ions to diffuse to the interior of the axon.
The normal "polarized" state of -90 mv is immediately neutralized by the inflowing positively charged sodium ions, with the potential rising rapidly in the positive direction.
This is called depolarization. In large nerve fibers, the great excess of positive sodium ions
moving to the inside causes the membrane potential to actually "overshoot" beyond the zero level and to become somewhat positive.
In some smaller fibers, as well as in many central nervous system neurons, the potential merely approaches the zero level and does not overshoot to the positive state.
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3. Repolarization Stage.: Within a few 10,000ths of a second after the membrane
becomes highly permeable to sodium ions, the sodium channels begin to close and the potassium channels open more than normal.
Then, rapid diffusion of potassium ions to the exterior re-establishes the normal negative resting membrane potential.
This is called repolarization of the membrane. K+ channels are slow to open and slow to close. This causes
the VM to take a brief dip below resting VM. This dip is the undershoot and is an example of hyperpolarization
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Phases of action potential
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Phases of action potential
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A. RMP: causes
B. Depolarization: ionic causes
C. Repolarisation: ionic causes
Action potential cont…..d• If membrane potential(VM)reaches
threshold, Na+ channels open and Na+ influx =depolarizing the cell and causing the VM to increase. This is the rising phase of an AP.
• Eventually, the Na+ channel will have inactivated and the K+ channels will be open.
• Now, K+ effluxes and repolarization occurs. This is the falling phase.
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Events during an action potential
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Role of action potentials in the transmission of a nerve impulse.
A STMULUS causes the Na+ gated channel proteins to open which allows Na+ ions to diffuse down the concentration gradient across the membrane into the cell and so set off an action potential.
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Voltage-Gated Sodium and Potassium Channels
The necessary actor in causing both depolarization and repolarization of the nerve membrane during the action potential is the voltage-gated sodium channel.
A voltage-gated potassium channel also plays an important role in increasing the rapidity of repolarization of the membrane.
Voltage-Gate The voltage-gated sodium channel has two gates-one near
the outside of the channel called the activation gate, and another near the inside called the inactivation gate.
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They have 2 gatesAt rest, one is closed (the activation gate) and the other is
opened (the inactivation gate).Suprathreshold depolarization affects both of them.
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2
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Activation of the Sodium Channel When the membrane potential becomes less negative than
during the resting state, rising from -90 millivolts toward zero, it finally reaches a voltage-usually somewhere between -70 and -50 millivolts-that causes a sudden conformational change in the activation gate, flipping it all the way to the open position.
This is called the activated state; during this state, sodium ions can pour inward through the channel, increasing the sodium permeability of the membrane as much as 500- to 5000-fold.
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Initiation of the Action Potential
A Positive-Feedback Cycle Opens the Sodium Channels. First, as long as the membrane of the nerve fiber remains
undisturbed, no action potential occurs in the normal nerve.
However, if any event causes enough initial rise in the membrane potential from -90 mv toward the zero level, the rising voltage itself causes many voltage-gated sodium
channels to begin opening.
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Initiation of the Action Potential cont……d This allows rapid inflow of sodium ions, which causes a
further rise in the membrane potential, thus opening still more sodium channels and allowing more streaming of sodium ions to the interior of the fiber.
This process is a positive-feedback cycle , Continues until all the voltage-gated sodium channels
have become opened. Then, within another fraction of a millisecond, the rising
membrane potential causes closure of the sodium channels as well as opening of potassium channels, and the action potential soon terminates.
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Threshold for Initiation of the Action Potential:
• An action potential will not occur until the initial rise in membrane potential is great enough to create the vicious cycle described in the preceding paragraph.
• This occurs when the number of Na+ ions entering the fiber becomes greater than the number of K+ ions leaving the fiber.
• A sudden rise in membrane potential of 15 to 30 millivolts usually is required.
• Therefore, a sudden increase in the membrane potential in a large nerve fiber from -90 millivolts up to about -65 millivolts usually causes the explosive development of an action potential.
• This level of -65 millivolts is said to be the threshold for stimulation.
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Propagation of the Action Potential
• An action potential elicited at any one point on an excitable membrane usually excites adjacent portions of the membrane, resulting in propagation of the action potential along the membrane.
• When a nerve fiber is excited in its mid-portion-that is, the mid-portion suddenly develops increased permeability to sodium, and there will be current flow from the depolarized areas of the membrane to the adjacent resting membrane areas.
• That is, positive electrical charges are carried by the inward-diffusing sodium ions through the depolarized membrane and then for several millimeters in both directions along the core of the axon.
• This transmission of the depolarization process along a nerve or muscle fiber is called a nerve or muscle impulse.
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Propagation of Action Potential
1. Continuous (sweeping) conduction (occurs in unmyelinated axons) In this situation, the wave of de- and repolarization simply
travels from one patch of membrane to the next adjacent patch.
APs moved in this fashion along the sarcolemma of a muscle fiber as well.
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2. Saltatory (jumping) conduction (occurs in myelinated axons)
• Recall that the myelin sheath is not completed. There exist myelin free regions along the axon, the nodes
of Ranvier.• The wave of depolarization and repolarization jump from
nodes of Ranvier to nodes of Ranvier
Advantages Increase speed of transmission by 100 folds. Conserve energy as sodium-potassium pump only has to
operate at the nodes and fewer ions have to be transported124
Rates of AP Conduction Depends Upon
1. Level of myelinationFaster in mylinated than in unmyelinated
2. Size of nerve fiber Faster in large sized than in smaller ones
3. Age slower in babies and in elderly Maximum b/n the age 5-15 years
4. Temperature which affects the rate of diffusion and the rate of energy
release by respiration for active transport (since it is controlled by enzymes)
the consequence is that nerve impulse transmission is faster in endothermic animals which maintain a high body temperature.
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Properties of the action potential
Action potentials have a threshold: This is the minimum level of stimulus necessary to cause
depolarisation (i.e. open the ion channels) Action potentials have all -or -nothing principle:
Once an action potential has been produced at any point on the membrane of a normal fiber, the depolarization process travels over the entire membrane if conditions are right, or it does not travel at all if conditions are not right. This is called the all-or-none principle, and it applies to
all normal excitable tissues.
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Properties of the action potential cont....d Has refractory Periods During the time interval between the opening of the Na+
channel activation gate and the opening of the inactivation gate, a Na+ channel cannot be stimulated. This is called refractory period.
There are two types of refractory period:
1. Absolute refractory period (ARP)
2. Relative refractory period (RRP)
Absolute refractory period (ARP): Interval b/n the opening of the Na+ channel activation
gate and the opening of the inactivation gate. 2nd action potential can not be generated regardless of
the strength of stimulus.127
• ARP begins at the start of up stroke (the activated Na+ channels start as fast as possible) and extends into the downward stroke (Na+ channels are inactivated) .
• A Na+ channel cannot be involved in another AP until the inactivation gate has been reset.
Relative Refractory Period(RRP) New action potential can occur in an excitable fiber if the
stimulus is supra threshold The stimulus should be greater than normal b/c there are still
inactivated sodium channels and more K+ channels than normal are still open.
The RRP begins when the ARP ends.Reason:
Number of inactivated Na+ channels and Activated K+ channels during RRP.
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Graded Potentials also called receptor potentials Local changes in membrane potential Upon being stimulated, the dendrites of a neuron produce a
graded potential. Stimulation can occur in many ways, including chemical
stimulation (neurotransmitters, etc.), mechanical stimulation (certain pain receptors, hair receptor, etc.), light stimulation (photoreceptors) and a few other methods.
Magnitude of change is related to magnitude of triggering event
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Triggering event Triggering event causes a flow of ions across the membrane Leads to localized change in membrane potential Without constant triggering event, graded potentials will die
out Current is local – does not spread very far; and is small,
<10mV change Depending on the strength of the stimulus, can be changed to
AP usually on summation.
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Comparison between Graded potential and action potentials
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Graded potential Action potential Graded responses-Amplitude varies
with condition of the initiating events
All or none response; once a membrane is depolarized to threshold, amplitude is independent of the initiating event.
Graded responses can be summated Action potential can not be summatedHas no refractory period Has refractory periodIs conducted decrementally; amplitude decreases with distance
Not affected by distance
Duration varies Duration is constant with a specific cell under constant condition
Can be depolarization or repolariztion Is depolarization with an overshootInitiated by environmental stimulus (receptor) ,by NTs, or spontaneously
Initiated by membrane depolarization.
Synaptic Transmission Synapse is the junction b/n two cells in which one must be a
neuron. It is the site of transmission from one neuron to the next. Is site where neuron communicates with another cell:
(neuron or effectors) There 3 types of synapses
1. Neuroneuronal junction (presynaptic and postsynaptic neurons)2. Neuromuscular junction3. Neuroglandualr junction
There 3 types of neuroneuronal junctions i.e.o Axo-dendritic, o Axosomatic and o Axo-axonic junctions
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In autonomic NS, they are called ganglia (ganglion singular) Pre- synaptic structure is always a nervePost- synaptic structure can be:
• A nerve
• Muscle
• Gland
• Skin The post- synaptic structures are collectively called effector
organs or simply effectors.
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Synaptic Transmission Begins with the stimulation of a neuron.
One neuron may be stimulated by another, by a receptor cell, or even by some physical event such as pressure.
Once stimulated, a neuron will communicate information about the causative event. Such neurons are sensory neurons and they provide info
about both the internal and external environments.Sensory neurons (afferent neurons) will send info to
neurons in the brain and spinal cord. There, association neurons (interneurons) will integrate the
information and then perhaps send commands to motor neurons (efferent neurons) which synapse with muscles or glands.
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Thus, neurons need to be able to conduct information in 2 ways:From one end of a neuron to the other end (pre and post
synaptic neurons).Accomplished electrically via APs
Across the minute space separating one neuron from another (synapse)
Accomplished chemically via neurotransmitters. One neuron will transmit information to another neuron or to a
muscle or gland cell by releasing chemicals called neurotransmitters.
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The site of this chemical interplay is known as the synapse.An axon terminal (synaptic knob) will adjoin another cell, a
neuron, muscle fiber, skin, or gland cell.This is the site of transduction – the conversion of an
electrical signal into a chemical signal.
Mechanism of transmission An AP reaches the axon terminal →open VG-Ca2+ channels
→Ca2+ rushes in and binds to regulatory proteins → initiation of NT exocytosis.
NTs diffuse across the synaptic cleft bind to receptors on the postsynaptic membrane → initiation of some sort of response on the postsynaptic cell.
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Mechanism of transmission
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Mechanism of Synaptic Transmission• An AP reaches the presynaptic axon terminal of the
presynaptic cell and causes V-gated Ca2+ channels to open.
• Ca2+ rushes in, binds to regulatory proteins & initiates NT release by exocytosis.
• NTs diffuse across the synaptic cleft and then bind to specific receptors on the postsynaptic membrane and initiate postsynaptic potentials.
• NT-receptor interaction results in either EPSP or IPSPDifferent neurons can contain different NTs. Different postsynaptic cells may contain different
receptors.Thus, the effects of NT can vary.
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Mechanism of Synaptic Transmission When the NT-R combination triggers the opening of
ligand-gated Na-channels, this leads to membrane depolarization, EPSP. E.g. Ach on Nicotinic receptor
When the NT-R combination triggers the opening of ligand gated K+ or Cl- channels, this leads to membrane hyperpolarization, IPSPe.g. GABA on GABAb receptor
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Graded depolarization Bring the neuronal VM closer to threshold. Thus, it’s often referred to as an excitatory postsynaptic potential or EPSP.
Graded hyperpolarization Bring the neuronal VM farther away from threshold and thus are referred to as inhibitory postsynaptic potentials or IPSPs.
EPSPs & IPSPs
Summation• One EPSP is usually not strong enough to cause an AP• However, EPSPs may be summedA. Temporal summation
The same pre-synaptic neuron stimulates the postsynaptic neuron multiple times in a brief period.
The depolarization resulting from the combination of all the EPSPs may be able to cause an AP.
B. Spatial summationMultiple neurons all stimulate a postsynaptic neuron
resulting in a combination of EPSPs which may yield an AP
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Neurotransmitter Removal NTs are removed from the synaptic cleft via:
Enzymatic degradationDiffusionReuptake
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Properties of synaptic transmission1. Unidirectional conduction2. Synaptic delay (0.5 -1.0m/s)3. Fatigue -↓in response of postsynaptic neurons after repetitive
stimulation by the presynaptic neurons 4. Synaptic potentiation (facilitation):– persistence of out put
signals after the stoppage of in put signal
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Factors Affecting Synaptic transmission pH
Alkalosois ↑ Synaptic transmissionAcidosis ↓ Synaptic transmission
Hypoxia ↓ Synaptic transmission Drugs
Caffeine, theophylline, theobromine ↑ Synaptic transmission
Strychinine ↑ Synaptic transmissionHypnotics, anesthtics, tranquilizers ↓ Synaptic transmission
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