Basics on Neurophysiology

[02]: Neurophysiology 1Dr. Darwin Dasig20 Aug 2014

Physio 21

COLLEGE OF ALLIED MEDICAL PROFESSIONSUniversity of the Philippines Manila

Bachelor of Science in Physical Therapy Class of 2017

TopicsI. The Nervous systemII. Resting membrane potentialIII. Local potentialIV. Action potential or Nerve impulseV. Synapse and Synaptic transmissionVI. Somatosensory system

I. THE NERVOUS SYSTEM It is used for:

Control of the body. Integration

Integrates all the systems in order to maintain homeostasis

It is Contralateral. It senses danger from the external

environment and reacts accordingly in the other direction

The right brain controls the left side of the body and vice-versa

It interacts with the internal and external environment in order to maintain homeostasis.

It is composed of the Brain, Brain stem, Spinal cord, nerves and muscles.

Brain Serves many different functions. It is comprised of Neurons.

These are the functional part of the brain.

It has a Cell Body (Soma). Contains the nucleus. Metabolic center of the cell. Controls all the

maintenance of the neuron. It has several processes

called Dendrites which extend outward and becomes a receptive area for an adjacent axon.

It also has a long process called an Axon that originates from the Axon Hillock.

Action potentials / Conducted impulses

generate in the initial segment of the axon.

This divides into presynaptic terminals, each of which ends in a number of synaptic knobs/terminal buttons or boutons.

Can be classified into unipolar, bipolar, or multipolar.

Axons can end either on another neuron or into an effect organ.

Neurons function via: Electrical signals

Local potential Nerve impulse/Action

Potential Chemical signals

Synaptic transmission Works in an All/None

Response

II. RESTING MEMBRANE POTENTIAL In order generate a potential difference

across the membrane of the cell, there are two conditions that must be met. There is an unequal distribution

of ions of one or more species across the membrane (Concentration gradient).

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[02]: Neurophysiology 1Physio 21UPM PT 2017

The membrane must be permeable to one or more ions. Permeability is provided by the

presence of channels that may be open or closed via voltage gauge.

The resting membrane potential of any neuron is usually -70mV.

Plasma membrane Composed of Phospholipids.

Phospholipids have polar head (Hydrophilic) and 2 non-polar tails comprised of fatty acyl chains (Hydrophobic).

They are amphiphatic. Can combine to form a circular

shape with the hydrophilic head on the outside or into a more stable lipid bilayer with the heads on the outside. This formation would not

allow charged/polar molecules to cross the lipid bilayer.

Structural proteins are present in order to allow charged or large particles to pass through.

Small and non-charged particles are the only ones able to pass through this bilayer.

The permeability of the membrane for ion species (K+,Na+,Cl-) contribute to the charge of the resting membrane potential. K+ ions are intracellular. Na+, Cl- ions are

extracellular. No Na+ leak channels are

present (Voltage gauged only).

K+ and Cl- can move freely through the plasma membrane.

Gibbs-Donnan Equilibrium

“In the presence of a non-diffusible ion, diffusible ions distribute themselves so that at equilibrium, their concentrations are equal.”

This is affected by the concentration and electrical gradient.

K+ and Cl- ions can move freely through the membrane. But negatively charged proteins that are present in the membrane prevent Cl- ions from moving inward, resulting in their extracellular nature.

[K + ] i = [Cl - ] o

[K+]o [Cl-]i Donnan Effect

Refers to the asymmetric distribution of permeant ions at equilibrium.

Electrical difference across the membrane with magnitude is determined by Nernst equation.

Transmembrane Potassium Ion Gradient thru Non-Gated Potassium Ion Leak Channels Nernst equation

Diffusion Pressure Wd = RT (ln[C]hi – ln[C]lo)

Electric Pressure We = (Em) (Zi) (F)

Em= absolute membrane potential; Zi = valence (number of charges on the



ion); F = faraday (number of coulombs per mol of ion)

At equilibrium: There is no net

movement. Diffusion pressure =

Electrical pressure. This is used to determine the

equilibrium potential of a single diffusible ion (The potential dictates the direction of the motion that the ions follow to attain equilibrium). K+ = - 90 mV

Moves outside via leak channels.

Na+ = + 60 mV Moves inward via

gated channels. Cl- = - 70 mV

No net movement. In equilibrium with the

RMP* Leak channels allow free movement of

the ion* The Membrane potential at rest depends primarily on the transmembrane potassium ion gradient thru non-gated potassium ion leak channels

K+ leak channels Open and closed voltage-gauged

channels K+ ions can move freely but the RMP

doesn’t reach the equilibrium potential of K+ because Na+ can move and leak In the membrane in small quantities

Na+ ions has no leak channels only voltage-gauged channels are present

Resting membrane potential via Goldman Constant field equation This equation takes into account all the

permeabilities of the ions present in and out of the cell.

Takes into account the concentration ratios of each of the ions.

*K+ moves out freely allow the RMP to move to -90mV while Na+ ions move inward in small quantities to revert the RMP back to -70mV.

Na+-K+ ATPase pump

Converts ATP to ADP and P to actively transport 3 Na+ ions out and 2 K+ ions in which results in a net loss of +1 charge inside the cell.

This maintains the difference in concentration of Na+ and K+ and the negativity of the inside of the cell.

Most important part of the RMP. The asymmetry of the concentrations

results in the electric charge.



The resting membrane potential is not in equilibrium. The RMP is only a steady state due to

the presence of the ATPase pump. Due to the usage of ATP (Equilibrium

doesn’t need energy in order to be maintained).

III. LOCAL POTENTIAL Local Potential

Transient shift of the membrane potential in a localized area of the cell (quick change).

Change in one portion of the membrane (any kind of change).

Lygan change – a neurotransmitter combines with receptor that opens (synaptic potential).

Graded response – amplitude is proportional to size of stimulus (more to more).

Hyperpolarization ↔ depolarization (hyper = increase negativity)

Rapid ↔ long

Local Potential Kickoff Local change in permeability of the

membrane to 1 or more ions. Synaptic potential

Lygan change Generator potential

chemical change Change in voltage/current applied from a

source. Electrotonic potential

Add voltage *increase Na and K conductance =

depolarization due to high driving force of Na (lesser degree when increased Na conductance).

Local Potentials Change in potential develops and subsides

over a few milliseconds. Remain localized in region where stimulus

is applied. Not sharply confined: falls off over a finite

distance on the membrane. Within milliseconds and within a single

area. Voltage change = current X resistance Some ions leak out across membrane.

• Lesser charges reach more distant sites.

• stable resistance : decreased current → decreased voltage

Local potential (Voltage change) – decreases with distance from the point of stimulation

Space constant



Describes the distance of the voltage change along the membrane.

Distance at which the initial transmembrane voltage change has fallen to 37% of its peak value.

The larger the space constant, the farther along the membrane a voltage change is observed after a stimulus is applied.

Limit of the local potential (distance away the body).

λ=√Rm /RaRm = transmembrane resistance (ohm-cm) Ra = internal axoplasmic resistance

(ohm/cm)

↑ Diameter of axon or dendrite• ↓ Ra (internal axoplasmic

resistance)• ↑ space constant • ↑ current will flow farther along

cell↑ Rm (transmembrane resistance)

• ↑ space constant• less current leaks out

Directly related to the transmembrane resistance.

High transmembrane resistance – longer distance (how easy to leave; barrier will squish them out).

Low Internal axoplasmic resistance – high distance (how easy to travel; inside is very spacious).

Local Potentials CAN BE SUMMATED! Spatial summation

Add up beside each other (through space).

Remain localized in region where stimulus is applied.

Not sharply confined: falls off over a finite distance on the membrane.

Temporal summation Change in potential develops and

subsides over a few milliseconds. Same space (through time) Repeated stimulation

*Spatial summation (top) and temporal summation (bottom)*summated subthreshold potentials may reach threshold and produce an action potential*neurons = electrical and chemical communication

IV. Action potential or Nerve impulse ACTION POTENTIAL

Fleeting, self-renewing wave of membrane depolarization that propagates without decrement along the length of a nerve axon at high speed.

Is a rapid, all-or-none change in the membrane potential followed by a return to the resting membrane potential.

Voltage-dependent ion (Na+ and K+) channels in the plasma membrane are the basis for action potentials.



An action potential is propagated with the same shape and size along the entire length of an axon.

Action potentials are usually initiated at the axon hillock of the axon.

The action potential is the basis of the signal- carrying ability of nerve cells.

The patterns of conducted action potentials encode the information conveyed by nerve cells.

Spike Potential Sharp rise and rapid fall of the membrane

potential.

Refractory Period Absolute

Threshold to one-third of repolarization.

No stimulus will excite the nerve. Relative

Up to start of after-depolarization. Stronger than normal stimulus can

cause excitation.



After-depolarization Slower fall at end of spike potential. supernormal period

After-hyperpolarization Overshooting of membrane repolarization

after reaching resting level. subnormal period

All or None Law Full-pledged AP produced once threshold

intensity is reached. Further increase in intensity of stimulus

does not produce increment or other change in AP.

No AP if stimulus is subthreshold in magnitude.

Constant amplitude and form.

Speed of Action Potential Propagation diameter of axon

*↑ diameter → ↓cytoplasmic resistance → ↑ flow of ions → ↑length of axon depolarized (↑space constant) → ↓time needed for AP to travel along axon

myelin ↑ effective resistance of axonal

membrane (transmembrane



resistance Rm): ions must flow through myelin before reaching ECF

↑ space constant ↓ effective capacitance of axonal

membrane: ↑distance between ICF & ECF

↓ time constant ↑ conduction velocity

unmyelinated axons Voltage gated Na+ and K+ ion

channels distributed uniformly along length of axonal membrane.

myelinated axons High concentration of voltage-gated

Na+ and K+ ion channels in axon hillock & nodes of Ranvier.

low density along internode

Saltatory Conduction Myelinated axons

myelinated: axons > 1μm diameter conduction velocities:myelinated = 3 –

120 m/sec; unmyelinated = 0.5 – 2.0 m/sec

V. SYNAPSE AND SYNAPTIC TRANSMISSION Synapse - A junction where the axon or

some other portion of one neuron (called the presynaptic neuron) terminates on the dendrites, soma, or axon of another neuron (called the postsynaptic neuron), muscle cell, or gland cell.

Types of Synapses Electrical

There is a gap junction formed between the presynaptic and postsynaptic neuron.

There is cytoplasmic continuity. Since the neurons are connected to

each other, they are inflexible (they cannot form new connections).

Each gap junction is formed by two hemichannels called Connexons, one contributed by each cell.

The gap junction forms low-resistance bridges through which ions pass with relative ease.

There is very little distance between the two neurons (3nm-5nm).

Ionic currents travel extremely fast through these bridges.

There is no synaptic delay. The structure allows for the

bidirectional travel of the ionic currents.

Uses very little metabolic energy and molecular machinery.

Highly reliable.



Chemical Presynaptic and postsynaptic neurons

are separated by a space called the Synaptic Cleft. There is no cytoplasmic continuity. Since the neurons are separated

from each other, they are flexible (they can form new connections as required, such as when learning new skills or remembering something). This is termed “Plasticity.”

The presynaptic neuron uses chemical transmitters called Neurotransmitters that bind to the postsynaptic neuron to propagate potentials.

Neurotransmitters are able to travel much larger distances (30nm-50nm) between the presynaptic and postsynaptic neuron.

The neurotransmitter is unidirectional: from the presynaptic neuron to the postsynaptic neuron.

They are capable of amplifying or inhibiting signals.

They can transmit information over a broad time domain.

They exhibit Plasticity. Refers to the synaptic strength

function of recent neural activity. It plays a role in learning and

memory. Essential to the success of the

vertebrate species.

Kinds of Synapses Based on Location Inhibitory synapses – nearer to the axon

hillock Axo-somatic (axon to the soma) –

most inhibitory Excitatory synapses – near the dendrites

Axo-dendritic (axon to a dendrite) – most excitatory

Axo-axonal (axon to another axon) Dendro-dendritic (a dendrite to another

dendrite; rare) Soma-somatic (the soma to another

soma; rare) Dendro-somatic (a dendrite to a soma)

Neurotransmitters Stored in synaptic vesicles. Released into the synaptic cleft with the

nerve impulse. Act on appropriate receptors on the

postsynaptic membrane.



Different Neurotransmitters Small-molecule transmitters

Monoamines (Acetylcholine, Serotonin, Histamine)

Catecholamines (Dopamine, Epinephrine, Norepinephrine)

Amino Acids (Glutamate, GABA, Glycine)

Large-Molecule transmitters Neuropeptides (Substance P,

Enkephalin, Vasopressin) Glutamate – The main excitatory

transmitter. GABA (Gamma-Aminobutyric Acid) – The

main inhibitory transmitter. Neuromodulators

Chemicals released by neurons with little or no direct effects on their own, but can modify the effects of neurotransmitters.

Transmitter Release Mechanism

The action potential opens voltage-gated Ca2+ channels at the end of the axon.

The axon allows Ca2+to enter. This increases the

Ca2+intracellular concentration. The increased Ca2+ level triggers

the binding of synaptic vesicles to the membrane.

The neurotransmitters inside the synaptic vesicles are then released to the synaptic cleft via exocytosis.

Various Structures Involved Synaptotagmin

The synaptic vesicle’s Ca2+sensor.

It binds proteins that cause the vesicles to dock and bind to the presynaptic terminal membrane.

SNAREs These are tethers employed

by the synaptic vesicle and the presynaptic neuron’s cell membrane to ensure that the vesicle reaches the cell membrane.

Vesicle SNARE (v-SNARE) Synaptobrevin

Terminal membrane SNARE (t-SNARE) Syntaxin SNAP-25

Snare Mechanism Initial State

The vesicle moves to the nerve terminal membrane, which contains Syntaxin and SNAP-25 (t-SNAREs).

Formation of the Ternary Complex of Snares N-sec-1 (a protein in

Syntaxin), dissociates from Syntaxin. This allows the Syntaxin

and the SNAP-25 to form a complex.

The distal end of the Synaptobrevin begins to wind around the Syntaxin-SNAP-25 complex. This results in a ternary complex.

Tightening of the Ternary Snare Complex The three SNAREs continue to

form a tight bundle of helices. The vesicle is further drawn to

the presynaptic membrane. Fusion and Exocytosis

The entry of Ca2+ via voltage-gated channels causes an influx of Calcium that binds to Synaptotagmin.

This triggers fusion of the vesicle and the cell membrane, and consequent exocytosis of the neurotransmitter.

Disassembly of the Ternary Snare Complex



α-SNAP and the ATPase NSF bind to the ternary SNARE complex.

They use the energy of ATP hydrolysis to disassemble the SNAREs.

Recycling of Snares The vesicle is endocytosed,

and the three SNAREs are again ready for use.

Additional Information Transmitter release is a

quantum. The number of

neurotransmitter molecules released by one vesicle is fixed.

Even if the neurotransmitters are quantized (Quantum Content), the number of quanta released when the synapse is activated depends on the level of Ca2+.

The greater the Ca2+, the more quantized neurotransmitters are released.

Burst of transmission terminates with rapid sequestration in organelles (such as the mitochondria) within the ending.

Ca2+is extruded via the Na+- Ca2+Antiport.

Neurotransmitter Receptors Ionotropic Receptors

The chemical receptor is also the channel.

Ligand-gated ion channel proteins

Rapid opening of ion channels Depolarization and

hyperpolarization Nicotinic Acetylcholine, GABA,

Glycine, Serotonin, Glutamate Metabotropic Receptors

The chemical receptor is not the channel.

The cell membrane uses proteins to facilitate the channeling of the neurotransmitter.

Seven-transmembrane-helix-receptors

G protein-linked

G proteins are nucleotide regulatory proteins that bind GTP.

Ion channel proteins or 2nd

messenger effector proteins Translate signals to biological

effects inside the cell. Glutamate, Muscarinic

Acetylcholine, α and β adrenergic Excitatory Postsynaptic Potential

(EPSP) Local potential of depolarization under

the active zone from a single stimulus. Increases the excitability of the neuron

to other stimuli. Ionic basis:

Na+ channels are opened. There is an increase in Na+

conductance through ligand-gated channels.

Closure of K+ channels. Inhibitory Postsynaptic Potentials

(IPSP) Local potential of hyperpolarization Postsynaptic direct inhibition. Stimulation to other stimuli is decreased. Ionic basis:

Opening of CI- channels. There is an increase in Cl-

conductance causing an outward flow of current.

Opening of K+ channels. Closure of Na+ or Ca2+ channels.

Excitation Spatial and Temporal summation.

Spatial summation refers to excitation over an area, where intersecting areas of excitation in the postsynaptic neuron are added-up.

Temporal summation refers to repeated excitation over time.

The axon hillock is the area of highest integration

Inhibition Presynaptic Inhibition

Provides a mechanism for controlling the efficacy of transmission at individual synapses.



Mediated by Axo-axonal synapses.

Postsynaptic Inhibition Direct Inhibition

Inhibition with IPSP Not a consequence of

previous discharges of the postsynaptic neuron.

Indirect Inhibition Due to the effects of previous

postsynaptic neuron discharge (refractory period or during after-hyperpolarization).

Long-term Potentiation Characterized by the enhanced

transmission at synapses that follow high frequency stimulations.

First observed in the hippocampus, a part of the brain that plays an important role in memory.

Depends on the presence of NMDA (N-methyl-D-aspartate) receptors in the postsynaptic membrane.

Plays a role in memory and associative learning.

Convergence and Divergence One to one. Divergence:

One to many – The axon of the presynaptic neuron divides into many branches that end on many postsynaptic neurons.

Spatially focused – The branching is much less, usually confined to several effectors in close proximity.

Widely divergent – The branching goes over a wide area.

Convergence: Many to one – Many presynaptic

neurons converge on a single postsynaptic neuron.

REFERENCES:

Barret, K.E., Barman, S.M., Biotano, S., & company. (2012). Ganong’s Review of Medical Physiology, 24th ed. The McGraw-Hill Companies, Inc., United States of America.

Dasig, D. (2014). CAMP Physio 21 Neurophysiology 1 2014 Power point presentation.

Koeppen, B.M., Stanton, B.A. (2012). Berne and Levy Physiology, 6th ed. Molsby Inc., Elsevier Inc.

Waxman, S.G. (2013). Clinical Neuroanatomy, 27thed. The McGraw-Hill Companies, Inc., United States of America.

Authors’ Notes on the Subject Matter




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Basics on Neurophysiology