BIOPHYSICS OF ACTION POTENTIAL & SYNAPSE

Ivan Poliaček

Excitable tissues - neuron (nerve tissue) - muscle fiber (muscle tissue)

Neuron - primary structural and functional unit of nerve tissue (brain, spinal cord, nerves, sensory cells)- 4 – 130 μm

soma

dendrite

nucleus

axon terminal

myelin sheath

axon hillockinitial segment

node of Ranvier

Schwann cell

Propagation of neuronal excitation from dendrites to the axon

dendrites

soma

axon with an axon collateral

Membrane potential, membrane depolarization,

hyperpolarization

Cell membrane - reminder

• double-layer of phospholipide + cholesterol + proteins

INTRA & EXTRA-CELLULAR ION CONCENTRATIONS

ion inside outside

(e.g. plasma)

Na+ 12 mM 145 mM

K+ 140 mM 4 mM

Cl- 4 mM 115 mM

HCO3 - 12 mM 30 mM

protein - 140 mM 10 mMCa++ 0,0001 mM 2

mM

A magnitude is determined by concentrations & permeabilities

of membrane for potasium, chlorine and sodium

eCl.PiNa.PiK.P

iCl.PeNa.PeK.Pln.

F

T.RV

ClNaK

ClNaKm

P K+ , P Na+ , P Cl- - permeabilities for K+, Na+, Cl-

[K+], [Na+], [Cl-] - concentrations

Membrane potential - Goldman equation

What does keep these concentrations uneven?Is interior of the cell negatively charged?How can be membrane potential altered?What is responsible for permeability changes?How will changes in K+, Na+, Cl- permeabilities change membrane potential?What is term for lower MP – more polarized cell membrane?What is the term for higher MP – less polarized cell membrane?

Resting membrane potential for neuron - about -70 mV

100 : 4 : 45

Depolarization – less polarization = reduced magnitude of membrane potential (e.g. from -70 mV to -60 mV or more)

Hyperpolarization –

- more polarization = increased magnitudeof membrane potential(e.g. from -70 mV to -80 mV)

Graded (local) responses = graded depolarizationsor hyperpolarizations : - electricity - chemicals- generator potential (sensory)

- synaptic EPSP (depolarization) IPSP (hyperpolarization)

Neuronal recording

Rest # 1

SYNAPSEneurons signal to each other or to muscles or glands

• Electrical synapses – electric signalgoes through„gap junction“(bidirectional)

• Chemical synapses – chemical transmission (one-way) one-directional from a presynaptic to a postsynaptic cell

1 mm3 of human cerebral cortex - about a billion of synapses

Axo-dendritic synapses

Synapses:

- axo-dendritic - axo-somatic- axo-axonal

neuron

Action potential comes via axon to the terminal at pre-synaptic membrane

1. depolarization opens voltage gated Ca channels - Ca++ diffuse into neuron

2. Ca++ inside - vesicles towards the membrane (proteins stenine and neurine) - exocytosis – release of neurotransmitter (mediator) in the synaptic cleft

Synaptic transmission

3. diffusion of mediator molecules through the cleft (30-50 nm)

4. mediator molecules activates receptors on subsynaptic part of postsynaptic membrane

Synaptic transmission

IONOTROPIC receptors

– ligand-gated channels producing

EPSP or IPSP at post-synaptic cell

METABOTROPIC receptors

– mediator at extracellular domain activates intracellular G-proteine leading to the intracellular signaling (gene expression, chemical reactions, channels opening / closing – membrane permeability changes)

Summary:

- action potential

- voltage gated Ca channels

- Ca++ influx

- vesicles exocytosis

- neurotransmitter (mediator) release

- its diffusion through the cleft

- interaction with receptors (e.g. ligand gated channels)

How does action stop?elimination of neurotransmitter- reabsorbed by the presynaptic cell (re-packaged into vesicles)- broken down metabolically- diffused away

Neurotransmitters chemically : aminoacids (glutamate, GABA, aspartate, glycine),

peptides (vasopresin, somatostatine, neurotensine,...),monoamines (norepinephrine, serotonine, acetylcholine,...)

Excitatory :- acetylcholine (neuromuscular junction)- glutamate

Inhibitory :- GABA- glycine (spinal reflexes)

excitation – inhibition mostlydetermined by receptor

In the brain are essential: glutamate and GABA

Rest # 2

Comments and requests are welcomed.

Why are chemical synapses called chemical?What ion initiates synaptic transmission?Where is neuromediator stored?Where is it released?Where does neurotransmitter act?What is main difference between metabotropic receptor and ligand gated channel?What is the difference between ligand gated and voltage gated channel?Where are amployed ligand and where voltage gated channels in the synaptic transmission?

Summation of postsynaptic potentials (stimulation of several synapses with ligand gated ion channels)

EPSP – excitatory post-synaptic potentialthat depolarize

IPSP – inhibitory post-synaptic potentialthat hyperpolarize

Higher magnitude of PSP ? more neurotransmitter (and more receptors), the membrane already partially depolarized, for how long is neurotransmitter available (it must be quickly removed from the cleft or inactivated)

Further from synapse (subsynaptic membrane) e.g. at axon hillock - less effect of PSP – it is GRADED and LOCAL electrical response that spreads with FALLOFF

SUMMATION of PSPs1 EPSP - rare to the threshold , but temporal summation of 2 EPSP

additive effect of many synaptic potentials at a neuron if :- the time span between the stimuli is short - temporal summation- they arrive at a given region of a neuron - spatial summation

SUMMATION of PSPs

1 EPSP - rare to the threshold , but

spatial summation of 2 EPSP

additive effect of many synaptic potentials at a neuron if :- the time span between the stimuli is short - temporal summation- stimuli arrive at several synapses of neuron - spatial summation

Synaptic integration

- The combining of EPSPs and IPSPs on a neuron.

- In order for an action potential = ACTIVATION to occur, the threshold depolarization has to be reached at initial segment = axon hillock = trigger zone

action potential arises at trigger zone = initial segment if the depolarization there reaches the threshold

dendrites

somaaxon with an axon

collateral

I recommend to search GOOGLE summation of postsynaptic potentials at the axon hillockAnimation 5.2 - Summation of Postsynaptic Potentials

and see the followinghttp://sites.sinauer.com/neuroscience5e/animations05.02.html

Suggestions what is important and how to remember that important are appreciated, aren’t they?

Rest # 3

ACTION POTENTIAL

Action potential (nerve impulse) - at excitable conductive tissues = nerve fibers & muscle cells if depolarization reaches the gate threshold = firing level.

It is all-or-none (it happens or do not happen).

stimulation

rising phasedepolarization

falling phaserepolarization

hyperpolarization

- Local (graded) depolarization to the threshold - firing level - Na channels open (voltage gated) - Na+ influx - rapid depolarization

- SPIKE - even transpolarization – positive charge at internalside of membrane for a short moment (and negative outside) - Na channels close(voltage gated) andK channels open (voltage gated) –Na+ influx STOP + K+ efflux -rapid repolarization

500 times Na permeability At rest permeabilites for K+ : Na+ : Cl-

100 : 4 : 45At spike depolarization 100 : 2000 : 45

threshold and rising phase – Na channels are opening

the peak – Na+ permeability maximal, Na channels slowly shut off – transpolarization - till +30 mV

falling phase- Na channels inactivation, high voltage opens also voltage-sensitive K channels – potential towards resting level...

and even „overshooting“ it - (after)hyperpolarization

1 action potential requires high, but limited number of ions - consideringthe whole cell it is capable of producing many action potentials

What keeps the ion distribution appropriate?

• Each spike is followed by a refractory period.

• An absolute refractory period - it is impossible to evoke another action potential – during spike and right after it (Na channels are open and after that inactivated)

• A relative refractory period - a stronger than usual stimulus is required to evoke an action potential (hyperpolarization; part of Na channels recovered)

airway pressure

diaphragm EMG

expiratory neuron

exp

insp

expiratory neuron burstextracellular

spike

waveform

Rest # 4

Propagation of action potential

Local current spread

(electrotonic conduction) –

depolarization of nearbypart of membrane

- without the depression (an energy comes from the cell) along nerve or muscle fibers- a wave (a spot) of electrical negativity on the surface (electrical positivity on the internal site of membrane) due to openning and closing of voltage gated ion channels

Propagation of action potential – local currents

refractoriness

Saltatory conduction

from one node of Ranvier to the next one

orthodromicconduction

antidromicconduction

Electrical stimulation of nerve (muscle) fibers

Rheobase - minimal current amplitude of infinite duration (practically a few 100 ms) that results in an action potential (or muscle contraction)

Chronaxy (-ie) - minimum time over which an electric current double the strength of the rheobase needs to be applied, in order to stimulate a nerve cell (muscle fiber)

anode - higher polarization - lower excitability

cathode - depolarization- higher excitability

duration of electrical pulse [ms]

intensity of current [mA]

Summary• depolarization, repolarization, hyperpolarization• action potential – the shape, mechanisms• refractory periods• propagation of action potential (continual spreading,

saltatory conduction)• electrical stimulation – rheobase, chronaxy• graded potential• synapse, neurotransmitter, mechanisms of

transmission • receptors (ionotropic vs. metabotropic)• EPSP, IPSP, summation (temporal, spatial)• convergence, divergence

I will be pleased to take your requests and comments.

Please, let me know how to improve the lecture (and lecturer)

Thank you for your attention.