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SUMMARY

Physiology is one of the biological sciences which deals with the mechanisms of the normal functions of the living organism.

The property that living organisms can react (living cells can elicit an action potential) to stimuli is called excitability.

(excitatory response, inhibitory response)

The threshold : the smallest intensity of stimulus needed to elicit a minimal response (or an action potential)

The higher the threshold needed, the lower the excitability, vice versa. (index of excitability)

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REGULATION OF BODY FUNCTIONS: 1.Nervous regulation

Reflex, reflex arc, conditioned and unconditioned reflex 2. Humoral regulation

Telecrine, neurocrine, paracrine and autocrine 3. Auto-regulation Feedback

Negative feedback Positive feedback

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1) negative feedback1) negative feedback

The feedback signal produces an effect opposite to that of the control system.

Significance: maintaining homeostasis

2) Positive feedback

The feedback signal intensifies the activity of the control system.

significance ： accelerate the completion of a physiological process.

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CHAPTER TWOCHAPTER TWO

BASIC FUNCTIONS OF THE CELL

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HEADING INCLUDED IN THIS CHAPTER 1. Membrane structure and membrane

transport 2. Bioelectric phenomena of the membrane 3. The contraction of skeletal muscle.

CELL MEMBRANETransport of Substances Throughthe Cell Membrane

CELL MEMBRANE It is a protective sheath , enveloping the cell body. This membrane separates the fluid outside the

cell called Extracellular fluid (ECF) and the fluid inside the cell called Intracellular fluid (ICF).

The cell membrane is a semi-permeable membrane.

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I. THE STRUCTURE OF CELL MEMBRANE

Cell membraneCell membrane

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COMPOSITION OF CELL MEMBRANE

1. Proteins 55%

2. Lipids: 42%

phospholipids 25%

cholesterol 13%

other lipids 4%

3. Carbohydrates 3%.

LIPID BILAYER

Made of phospholipids Hydrophilic part of the molecule. Polar

Outside surface Hydrophobic part molecule. Non- polar

Inside the bilayer Found in cell- and organelle- membranes

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STRUCTURE OF PHOSPHOLIPIDS

Phospholipid: amphipathic moleculea polar hydrophilic phosphate head group: （ water soluble)

Two no-polar hydrophobic fatty chains: （ fat soluble)

THE LIPID BILAYER

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水 水 水 水 水 水 水 水水 水 水 水

水 水 水 水 水 水 水 水 水 水 水 水

水 水 水 水 水 水 水 水水 水 水 水 水 水 水 水

水 水 水 水水 水 水 水 水 水 水 水

Arrangement of phospholipids in cell membranes Forming a bilayer : the hydrophobic fatty acid chains in the middleThe hydrophilic groups are oriented toward the external and internal surfaces of the

membrane.

CELL MEMBRANE IS FLOWING

The flowing property depends upon the cholesterin .In the normal temperature, the phospholipids are in liquid state, so the most lipid and protein molecules are freely flow in the bilayer planes of cell membranes. But the flowingness is only limited in the same layer. That is to say that a molecule can only flow in its layer and can not go to the other layer. The flowing property depends upon the cholesterin. The higher the concentration of cholesterin, the slower the flowing rate. The flowing property is a protection for the membrane. If a part of membrane is injured, the cell membrane can repaired by membrane flowing.

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EffectsEffects::Carrier Carrier Channel Channel ReceptorReceptor

MEMBRANE PROTEINSMEMBRANE PROTEINS

The membrane contains large numbers extrinsic of protein molecules.There are two types of membrane proteins: the integral proteins and the

peripheral proteins.

① The integral proteins penetrate all the way through the membrane. The integral proteins provide structural pathways through which

water and water soluble substances, especially the ions, can diffuse between extra- and intracellular fluids.

② The peripheral proteins are attached to the surface of the membrane The extrinsic proteins interact with the membrane lipids

predominantly by charge interactions with the water-soluble polar head groups. They are either entirely or almost entirely on the inside of the membrane and normally attached to one of the integral proteins. These extrinsic proteins usually function as enzymes.

The protein molecules in the membrane have entirely different properties for transporting substances. Their molecular structures interrupt the continuity of the lipid bilayer, constituting an alternative pathway through the cell membrane. The membrane proteins is very important in the substance transport across the cell membrane. These protein can function as carrier, channel or receptor.

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MEMBRANE CARBOHYDRATES

There are small amounts of carbohydrates, which consist of short, branched chains of monosaccharides. If the chain covalently linked to the membrane proteins, which is called glycoprotein , if linked to the membrane lipids called glycolipid. Usually glycolipid and glycoprotein are located on the outside of the membrane and extend from the cell surface into the extracellular fluid.

STRUCTURE- FUNCTION RELATIONSHIP

Lipid bilayer: Is selectively permeable Will allow only certain substances to pass through this

membrane. e.g. lipid soluble, non polar substances e.g O2, CO2.

Will not allow water soluble polar substances. E.g. Na+, Cl-, K+, HCO3-, Mg+,

Proteins with in the membrane: Functions as channels and carriers to transport the

substances that can not pass through the membrane. Permeability also depends on size of the particle.

TRANSPORT ACROSS CELL MEMBRANE

Cell membrane; Characteristics:Selectively

permeable

TRANSPORT MECHANISMS

Channels = protein structures, pores Cross the membrane (trans-membrane proteins) Form a link between ECF and ICF

Carriers proteins

THE PROTEIN CHANNELS

The protein channels are distinguished by two important characteristics: (1) Selectively permeable to certain substances because of Shape or charge (2) Many of the channels can be opened

or closed by gates

FUNCTIONS OF CELL MEMBRANE Protective to the cytoplasm and the organelles. Selective Permeability. Absorptive functions. Excretory functions. Exchange of gases Maintenance of shape and size of the cell.

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TYPES OF MEMBRANE TRANSPORT: 1. Simple diffusion2. Facilitated diffusion

Carrier mediated diffusionChannel mediated diffusion

3. Active transportPrimary active transportSecondary active transport

4. Endocytosis5. exocytosis

SOME IMPORTANT PHYSIOLOGICAL PROCESSES: Diffusion Osmosis

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DIFFUSION

Diffusion is the net movement of particles from a place of high concentration to the place of lower concentration .

Driving force ： thermal motion

diffusion flux : The rate of substance crossing a membrane in a unit of time

= mol(mmol)/cm2/s

DIFFUSION All molecules and ions in the body fluids,

including water molecules and dissolved substances, are in constant motion

Movement of a substance across a membrane as a result of random molecular motion

Tendency to move from higher concentration to lower concentration gradient.

Gradients Concentration Electrical

EXAMPLES OF DIFFUSION

Perfume Sugar solution

DIFFUSION

Diffusion across the cell membrane: Simple diffusion Facilitated diffusion

SIMPLE DIFFUSION: DEFINITION

Kinetic movement of molecules or ions occurs through a membrane or membrane pores.

No carrier proteins required.

FACILITATED DIFFUSION

Movement of particles from higher to lower concentration

Requires interaction of a carrier protein. The carrier protein aids passage of the

molecules or ions through the membrane by binding chemically with them and shuttling them through the membrane in this form.

DIFFUSION

FACTORS AFFECTING DIFFUSION ACROSS A MEMBRANE

Concentration gradient across the membraneConcentration

gradient= C1- C2. Rate of diffusion α

concentration gradient across the membrane.

Increase concentration gradient will increase the rate of diffusion.

C1 C2

FACTORS AFFECTING DIFFUSION ACROSS A MEMBRANE Surface area of the membrane

Rate of diffusion α Surface area of membrane across which diffusion is taking place.

FACTORS AFFECTING DIFFUSION ACROSS A MEMBRANE Solubility in the membrane or permeability.

E.g Lipid soluble Vs. Lipid in-soluble substances: Lipid soluble substances can diffuse easily

through the cell membrane Lipid insoluble substances can’t diffuse easily

through the membrane.Conclusion: Lipid solubility is important

factor in determining diffusion through the cell membrane.

FACTORS AFFECTING DIFFUSION ACROSS A MEMBRANE

Thickness of the membraneRate of diffusion α 1/

Thickness Increased thickness

of the membrane will decrease the rate of diffusion.

FACTORS AFFECTING DIFFUSION ACROSS A MEMBRANE Molecular weight

Rate of diffusion α 1/ MW of a particle. E.g. MW of glucose > Na , so rate of diffusion of

glucose is less than Na across a membrane.

FACTORS AFFECTING DIFFUSION ACROSS A MEMBRANE

Rate of diffusion =

ΔP : Concentration gradient across the membrane..

SA : Surface area of the membrane.. SOL : Solubility in the membrane or permeability. T : Thickness of the membrane. MW : Molecular weight

MWd

SATPD

FACTORS AFFECTING DIFFUSION ACROSS A MEMBRANE

P: Concentration gradient across the membrane. The greater the concentration gradient, the greater the rate of diffusion.

SA : Surface area of the membrane. The greater the surface area, the greater the rate of diffusion.

SOL : Solubility in the membrane or permeability. The more soluble the substance, the faster it will diffuse. Generally CO2 diffuses faster across membranes than °2 because CO2 exhibits greater solubility.

T : Thickness of the membrane. The thicker the membrane, the slower the rate of diffusion,

MW : Molecular weight

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ONLY LIPID SOLUBLE SUBSTANCES CAN DIFFUSE ACROSS THE CELL MEMBRANE FREELY

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OSMOSIS:

passive diffusion of waterpassive diffusion of water

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OSMOSIS

Movement of water across a semi-permeable membrane.

Water will diffuse from a region of higher water concentration to a region of lower water concentration.

The water concentration of a solution is determined by the concentration of solute.

The greater the solute concentration, the lower the water concentration.

OSMOSIS

FOR OSMOSIS TO OCCUR

There should be : Membrane : Semi-permeable i.e. it will not

allow solute particles to move. Difference in concentration of water( Solutes)

So movement of water will occur from higher concentration of water to lower concentration of water.

OSMOSIS ILLUSTRATED

H2OH2O H2O

H2O

H2O

H2O

H2OH2O

H2O

H2O

H2OH2O

H2O

H2OH2O

H2OH2O H2O

H2O

H2O

H2O

H2OH2O

H2O

H2O

H2OH2O

H2O

H2OH2O

OSMOSIS ILLUSTRATED

H2OH2O H2O

H2O

H2O

H2O

H2OH2O

H2O

H2O

H2OH2O

H2O

H2OH2O

OSMOTIC PRESSURE

OSMOSIS (SUMMARY) When a substance is dissolved in water, the

concentration of water molecules in the solution is less than that in pure water, since the addition of solute to water results in a solution that occupies a greater volume than does the water alone. If the solution is placed on one side of a membrane that is permeable to water but not to the solute and an equal volume of water is placed on the other, water molecules diffuse down their concentration gradient into the solution . This process of the diffusion of solvent molecules into a region in which there is a higher concentration of a solute to which the membrane is impermeable—is called osmosis.

OSMOSIS ( SUMMARY)

The tendency for movement of solvent molecules to a region of greater solute concentration can be prevented by applying pressure to the more concentrated solution. The pressure necessary to prevent solvent migration is the osmotic pressure of the solution.

OSMOSIS.....

Depends on number of particles, not size of particles

Osmoles Miliosmols Osmolarity Osmolality

DEFINITIONS

An osmole is 1 gram molecular weight of un-dissociated particles eg 180 gms of glucose = 1 osmoleBut if the compound dissociates it gives more

particles and a greater osmotic effectE.g. 58.5 gm of NaCl = 1 gram mw = 2 osmoles

The osmolarity is the number of osmoles per liter of solution—eg,

Osmolality is the number of osmoles per kilogram of solvent.

Osmolality = osmoles per kg of solvent Osmolarity = osmoles per litre of solution

DEFINITIONS Tonicity is used to describe the osmolality of

a solution relative to plasma. Isotonic Solutions that have the same

osmolality as plasma Hypertonic; those with greater osmolality Hypotonic: those with lesser osmolality are

REVIEW

Cell membrane: characteristics Transport across the cell membrane Diffusion Osmosis

CARRIER MEDIATED DIFFUSION

CARRIER MEDIATED DIFFUSION

Carrier proteins transport molecules by changing shape. First, a molecule on one side fits the binding site, and by changing their configuration, the carrier can push the molecule to the other side of the membrane.

Carrier proteins are affected by temperature and can be saturated (that is, they "max-out" at a rate of transport because there is a finite number of transporter molecules in the membrane and a configuration change is needed for every transport event).

CARRIER MEDIATED DIFFUSION

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THE PROPERTIES OF CARRIER MEDIATED DIFFUSION :

(1) substrate specificity

(2) Saturation

(3) competitive inhibition

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Carrier

Cell membrane

A

B

SUBSTRATE SPECIFICITY

dextrose > levoglucose

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carrier

SATURATION

diffusion

Concentration of substrate

flux

For any transported solute there are a finite no. of specific carriers in a given membrane at any particular moment.

As the concentration of the solute to be transported is increased, the number of occupied binding sites increases until the carriers become saturated (i.e until all binding sites become occupied).

Transporter binding sites -> saturated ->No further flux even increase in solute concentration.

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Carrier

Cell membrane

A

B

COMPETITIVE INHIBITION

Although, both amino acid and sugar undergo mediated transport, a protein that transports aa does not transport sugars, and vice versa. However, a type of carrier transporting two different but similar solutes in the molecular structure may result in competitive inhibition.

EFFECTS OF THE FACILITATED DIFFUSION BY CARRIER:

Transporting nutrition substances

For example, glucose and amino acids

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CHANNEL MEDIATED FACILITATED DIFFUSION

CHANNEL MEDIATED FACILITATED DIFFUSION

Ions cross membranes via ion channels. As we know, integral membrane proteins can span

the lipid bi-layer. Some of these proteins form channels through which ions can diffuse across the membrane. A single protein may have a conformation similar to that of a doughnut, with a hole in the middle. This hole can act as the channel for ion movement.

The channel is just a pathway, the specific ion can diffuse through the channel from higher concentration side to the lower concentration side.

The diameters of protein channels are very small, only slightly larger than those ions passing through them. The small size of the channels prevents larger, polar, organic molecules from entering the channel.

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(1) THE IONIC SELECTIVITY

Channels blocker Na+ tetrodotoxin (TTX) Ca2+ verapamil K+ tetraethylammonium

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(2) THE STATES OF CHANNELS 1) Active (open) state ：

The channel is opened

2) Inactivated state ：The channel is closed and any stimulus can

not open it.

3) Resting state ： The channel is closed but stimuli

can open it.

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Na+ channel

K+ channel

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How do the states of channels How do the states of channels change?change?TYPES OF ION CHANNELS (GATE):

1. Chemically-gated channel

2. Voltage-gated channel

3. Mechanically-gated Channel

CHEMICALLY-GATED CHANNEL

The binding of specific molecules to channel proteins may directly or indirectly produce a change in the shape of the channel protein. Such channels are called chemically gated channel

VOLTAGED-GATED CHANNEL

Changes in the membrane potential can cause movement of the charged regions on a channel protein, altering its shape. This channel is called voltage-gated ion channel.

MECHANICALLY-GATED CHANNEL

Physically deforming (stretching) the membrane may affect the conformation of some channel proteins, which is called mechanically-gated ion channel.

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SIGNIFICANCE OF FACILITATED DIFFUSION MEDIATED BY CHANNELS

Transferring the signals across the cell membrane

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III) ACTIVE TRANSPORT

Concentration gradient geopotential gradient

High concentration

High concentration

diffusion

Active transport

downhill uphill

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DEFINITION OF ACTIVE TRANSPORTWhen a cell membrane moves molecules or ions uphill

across a membrane against a concentration gradient (or electrical or chemical gradient), the process is called active transport.

Active transport requires binding of a substance to the transporter in the membrane. Because these transporter moves the substance uphill, so often termed as “Pump”

Properties:1. Transport against concentration or

electrical gradient (or electrochemical gradient)

2. Metabolic energy must be expended

ACTIVE TRANSPORT

According to the source of the energy used to transport, the active transport is divided into

a. Primary Active transport (Energy is derived from breakdown of ATP.

b. Secondary Active Transport ( Energy is derived from the ion concentration difference across a membrane, which is already created by primary active transport.

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PRIMARY ACTIVE TRANSPORT

Primary active transport, also called direct active transport, directly uses energy to transport molecules across a membrane.

The energy is derived directly from breakdown of adenosine triphosphate(ATP)

NaNa ＋＋ /K/K ＋＋ pumppump

ATP USING PRIMARY ACTIVE TRANSPORT TYPES

P-type ATPase: sodium potassium pump, calcium pump, proton pump

F-ATPase: mitochondrial ATP synthase, chloroplast ATP synthase

V-ATPase: vacuolar ATPase

ABC (ATP binding cassette) transporter: MDR, CFTR, etc.

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NA ＋ /K ＋ PUMP ( NA ＋ /K ＋ -ATPASE)

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NA ＋ /K ＋ PUMP ( NA ＋ /K ＋ -ATPASE)

3Na+

2K+

ATP

ADP+Pi

Concentration gradient of NaConcentration gradient of Na ＋＋ and Kand K ＋＋

NaNa ＋＋

KK ＋＋

Extracellular (mmol)Extracellular (mmol) intracellular (mmol)intracellular (mmol)

145.0145.0

4.04.0

12.012.0

155.0155.0

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SIGNIFICANCY OF NA ＋ /K ＋ PUMP

1. Maintaining the Na+ and K+ concentration gradient across the membrane

2. Driving force of generation of bioelectricity

3. Driving force for the secondary active transport

4. Controlling the cell volume

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Ca2+ pump

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PROTON PUMP

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SECONDARY ACTIVE TRANSPORT Secondary active transport uses the energy

from an ion concentration gradient across the membrane which is previously established by a primary active transport process.

Secondary active transport or co-transport, uses energy to transport molecules across a membrane. In contrast to primary active transport, there is no direct coupling of ATP; instead, the electrochemical potential difference created by pumping ions out of the cell is used.

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TYPES OF SECONDARY ACTIVE TRANSPORT

Cotransport (Symport): The movement of actively transported solute is in the same

direction as sodium

Symport uses the downhill movement of one solute species from high to low concentration to move another molecule uphill from low concentration to high concentration (against its electrochemical gradient). The two species move in the same direction across the membrane

An example is the glucose symporter SGLT1, which co-transports one glucose (or galactose) molecule into the cell for every two sodium ions it imports into the cell. This symporter is located in the small intestines, trachea, heart, brain, testis, and prostate

Countertransport (Antiport): The movement of actively transported solute is

opposite the direction of sodium movement

In antiport two species of ion or other solutes are pumped in opposite directions across a membrane. One of these species is allowed to flow from high to low concentration which yields the entropic energy to drive the transport of the other solute from a low concentration region to a high one.

An example is the sodium-calcium exchanger or antiporter, which allows three sodium ions into the cell to transport one calcium out.

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IV ） ENDOCYTOSIS

Endocytosis is a process by which cells absorb molecules (such as proteins) by engulfing them.

It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane.

e.g. low density lipoprotein, transferrin, growth factors, antibodies and many others.

Types of endocytosis:1. Phagocytosis

- Phagocytosis (from Ancient Greek φαγεῖν (phagein) , meaning "to devour", κύτος,(kytos) , meaning "cell", and -osis, meaning "process") is the cellular process of engulfing solid particles by the cell membrane to form an internal phagosome byphagocytes and protists.

 Phagocytosis is involved in the acquisition of nutrients for some cells, and, in the immune system, it is a major mechanism used to remove pathogens and cell debris.

Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed.

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PHAGOCYTOSIS (CELL EATING)

the material contacts with the cell membrane

↓ the membrane invagination

↓ the invagination is pinched off

↓ leaving the engulfed material in the

membrane-enclosed vacuole ↓

the cell membrane intact

2. PinocytosisIn cellular biology, pinocytosis ("cell-drinking", "bulk-phase pinocytosis", "non-specific, non-absorptive pinocytosis", "fluid endocytosis") is a form of endocytosis in which small particles are brought into the cell, forming an invagination, and then suspended within small vesicles (pinocytotic vesicles) that subsequently fuse with lysosomesto hydrolyze, or to break down, the particles.

This process requires a lot of energy in the form of adenosine triphosphate, the chemical compound is mostly used as energy in the majority of cells.

Pinocytosis is used primarily for the absorption of extracellular fluids (ECF), and, in contrast to phagocytosis, generates very small vesicles.

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V ） EXOCYTOSISExocytosis (from Greek  exo is "out" and

English cyto- "cell" ) is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane and into the extracellular space.

These membrane-bound vesicles contain soluble proteins to be secreted to the extracellular environment, as well as membrane proteins and lipids that are sent to become components of the cell membrane. 

Exocytosis is the process of very large molecules or particles move out the cell.

Endoplasmic reticulum

protein

Golgi apparatus

vesicles

exocytosis

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EXOCYTOSIS

the endoplasmic reticulum ↓

particles ↓

Golgi complex ↓

the particles are packaged (secretory granules) ↓

these membrane-bound granules move along tracks of microtubiles to the cell membrane

↓ the granules and the cell membrane fuse

↓ the area of fusion breaks down

↓ leaving the contents of the granule outside the cell

↓ the cell membrane intact

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V ） EXOCYTOSIS

CaCa2+2+

CaCa2+2+

Both endocytosis and exocytosis require energy supplied by ATP, which belong to active transport.

Thank you!!!!!