BIOPHYSICS OF ACTION POTENTIAL

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BIOPHYSICS OF ACTION POTENTIAL SYNAPSE

• Ivan Poliacek
• Ján Jakuš

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Excitable tissues nerve tissue, muscle
tissueNeuron - 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
node of Ranvier
soma
Schwann cell
axon hillock initial segment
myelin sheath
nucleus
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Propagation of neuronal excitation from dendrites
to the axon
dendrites
soma
axon with an axon collateral
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Cell membrane - reminder

• double-layer of phospholipide cholesterol
  proteins
• isolating the cell from surroundings regulation
  of permeability communication (receptors and
  irritability)

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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
• proteín - 140 mM 10 mM

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Neuronal recording
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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)
Resting membrane potential polarization of the
cell membrane - interior of the cell is NEGATIVE
(neuron typically about 70 mV)
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ACTION POTENTIAL
rising phase depolarization
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).
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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)hyperpolariza
tion
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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
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closed open Bacterial
voltage-gated potasium channel
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Extracellular recording of respiratory neuron
exp insp

• airway pressure

diaphragm EMG
expiratory neuron
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expiratory neuron burst
extracellular spike waveform
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• 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)

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Scheme of Na voltage gated channeland K voltage
gated channel involved in processing of action
potential
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Propagation of action potential
Local current spread (electrotonic conduction)
depolarization of nearby part of membrane can
initiate the spike
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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
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Saltatory conduction
orthodromicconduction
from one node of Ranvier to the next one
antidromicconduction
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Electrical stimulation of nerve fibers
(intensity of current mA)
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)
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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)

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Axo-dendritic synaptic terminals chemical
synapses
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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)

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Types of neurotransmitter Aminoacids
glutamate, GABA, aspartate, glycinePeptides
vasopresin, somatostatine, neurotensine...Monoami
nes norepinephrine, dopamine, serotonione,
and acetylcholine Crucial neuromediatiors
in the brain are glutamate and GABA
RECEPTOR is mostly responsible for the effect
not the neurotransmitter itselfExcitatory
- acetylcholine - ACh (neuromuscular junction
- e.g. voluntary movement) -
glutamateInhibitory - GABA - glycine (spinal
reflexes)
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• 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 post-synaptic cell graded
  (post-synaptic) potential occurs
• - fast postsynaptic actions (synaptic delay
  usually 1-5 ms)

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• 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
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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)

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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
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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.
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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