BIOPHYSICS OF ACTION
POTENTIAL & SYNAPSE
Ivan Poliaček
Ján Jakuš
Excitable tissues – nerve tissue, muscle tissue
Neuron
- primary structural and functional unit of nerve tissue
(brain, spinal cord, nerves, sensory cells)
- 4 – 130 μm (soma – proteosyntesis, dendrites –
input, axon – output)
dendrite
axon terminal
soma
node of
Ranvier
axon hillock
initial segment
nucleus
Schwann cell
myelin sheath
Propagation of neuronal excitation from
dendrites to the axon
dendrites
soma
axon with an
axon collateral
Cell membrane - reminder
• double-layer of phospholipide + cholesterol + proteins
• isolating the cell from surroundings + regulation of permeability
+ “communication” (receptors and irritability)
INTRA- & EXTRACELLULAR ION
CONCENTRATIONS
ion
inside
outside
(e.g. plasma)
Na+
K+
ClHCO3 proteín -
12 mM
140 mM
4 mM
12 mM
140 mM
145 mM
4 mM
115 mM
30 mM
10 mM
Neuronal
recording
Resting membrane potential – polarization of the cell
membrane - interior of the cell is NEGATIVE (neuron
typically about 70 mV)
Depolarization – reduction of the magnitude of
membrane potential (e.g. from -70 mV to -60 mV or more)
Hyperpolarization – increase of the magnitude of
membrane potential (e.g. from -70 mV to -80 mV or more)
Efflux of K+ (through K channels), or influx of Cl– (through Cl channels)
rising phase
depolarization
ACTION POTENTIAL
falling phase
repolarization
stimulation
hyperpolarization
Action potential (nerve impulse) occures at excitable tissues
(mostly neuron fibers or muscle cells) when graded
potential reaches the threshold (gate threshold) –
firing level.
It is all-or-none (it happens or do not happen).
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
Only very small numbers of ions are involved
in 1 action potential considering the cell (axon) size
ratio of membrane permeability during rising phase of action potential –
perm K+ : perm Na+ : perm Cl- =
1 : 20 : 0.45
at quiet (resting membrane potential) =
1 : 0.04 : 0.45
closed
open
Bacterial voltage-gated potasium channel
Extracellular recording of respiratory
neuron
exp
airway
pressure
insp
diaphragm
EMG
expiratory
neuron
expiratory neuron burst
extracellular
spike
waveform
• Each action potential is followed by a refractory
period
• Refractory periods are caused by changes in the
state of Na and K channels
• An absolute refractory period - it is impossible
to evoke another action potential - Na channels
are "inactivated" at the end and immediately
after the spike - they cannot be made to open
regardless of the membrane potential
• A relative refractory period
- later, a stronger than
usual stimulus is required
in order to evoke
an action potential
(part of Na channels recovered)
Scheme of Na voltage
gated channel
and K voltage gated
channel involved in
processing of action
potential
Propagation
of action
potential
Local current
spread
(electrotonic
conduction) –
depolarization
of nearby
part of
membrane
can initiate
the spike
Propagation of action potential
refractoriness
- the duration around and below 1 ms
- without the depression (an energy comes from the cell)
- a wave (a spot) of electrical negativity on the surface
(electrical positivity on the internal site of membrane)
- openning and closing of voltage gated ion channels
orthodromic
conduction
Saltatory
conduction
from one node of Ranvier
to the next one
antidromic
conduction
(intensity
of current
[mA])
Electrical stimulation of
nerve fibers
anode - higher polarization
- lower excitability
cathode - depolarization
- higher excitability
(duration of electrical pulse [ms])
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)
SYNAPSE
neurons signal to each other and to muscles or glands
• Electrical
synapses
– electric signal
goes through
„gap junction“
(bidirectional)
• Chemical synapses – chemical transmission (one-way)
directionally from a presynaptic to a postsynaptic cell
(and are therefore asymmetric in structure and function)
human brain - 1014 to 5 × 1014 (100-500 trillion) synapses
(1 mm3 of cerebral cortex - about a billion of synapses)
Axo-dendritic
synaptic terminals –
chemical synapses
Synaptic transmission
• Action potential depolarizes pre-synaptic membrane
of synaptic terminal – Ca2+ influx through
voltage gated Ca channels
• Ca2+ activates proteins (stenine and neurine) attached to
vesicles (containing a neurotransmitter) – pulling the vesicles
to the membrane, making them to fuse with the membrane,
thereby opening the vesicles and dumping their
neurotransmitter contents (each vesicle contains thousands
molecules) into the synaptic cleft – exocytosis (active transport)
• Neurotransmitter molecules diffuse across the synaptic cleft
(30-50 nm between pre- and post-synaptic membrane)
and bind to receptors on the subsynaptic membrane ( it is a part
of post-synaptic membrane ) thus initiating the response (either
via G-protein coupled effector enzymes or via ligand gated ion
channels)
Types of neurotransmitter
Aminoacids : glutamate, GABA, aspartate, glycine
Peptides : vasopresin, somatostatine, neurotensine...
Monoamines : norepinephrine, dopamine, serotonione,
and acetylcholine
Crucial neuromediatiors in the brain are :
glutamate and GABA
RECEPTOR is mostly responsible for the effect
not the neurotransmitter itself
Excitatory - acetylcholine - ACh (neuromuscular
junction - e.g. voluntary movement)
- glutamate
Inhibitory
- GABA
- glycine (spinal reflexes)
Ionotropic receptors (ligand-gated ion channels) –
permeability changes e.g. efflux of K and/or influx of Ca
and Na on the subsynaptic membrane of the postsynaptic cell – graded (post-synaptic) potential occurs
- fast postsynaptic actions (synaptic delay usually 1-5 ms)
Metabotropic receptors (G-protein-coupled receptors)
- an extracellular domain binds to a neurotransmitter,
an intracellular domain binds to G-protein – the second
messenger (or intracellular messenger) – activated and
released from the receptor interacts with other proteins
e.g. with ion channels to open or close them (slow
postsynaptic response - ms to minutes)
ELIMINATION OF NEUROTRANSMITTER
due to thermal shaking, neurotransmitter molecules
eventually break loose from the receptors and drift away - reabsorbed by the presynaptic cell (re-packaged
in vesicles for future release)
- broken down metabolically
- difused away
EPSP – excitatory post-synaptic potential
that depolarize
IPSP – inhibitory post-synaptic potential
that hyperpolarize
The magnitude of a PSP depends on:
• the amount of neurotransmitter (and receptors)
• the electrical state of the postsynaptic cell (less
neurotransmitter is necessary if already partially depolarized)
• how long is neurotransmitter present in the synaptic cleft
(it must be quickly removed or inactivated)
SUMMATION of PSPs
1 EPSP
temporal
summation
of 3 EPSP
The effect of more than one
synaptic potential arriving
at a neuron is additive if :
- the time span between the stimuli is short - temporal summation
- they arrive at a given region of a neuron - spatial summation
Spatial summation of PSP
Synaptic
integration
- The combining of
excitatory and
inhibitory signals
acting on adjacent
membrane regions
of a neuron.
In order for an action
potential to occur,
the sum of excitatory
and inhibitory
postsynaptic potentials
(local responses) must
be greater than
a threshold value.
Summary
•
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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