BIOPHYSICS OF ACTION POTENTIAL

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BIOPHYSICS OF ACTION POTENTIAL SYNAPSE

• Ivan Poliacek

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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
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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Membrane potential, membrane depolarization,
hyperpolarization
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Cell membrane - reminder

• double-layer of phospholipide cholesterol
  proteins

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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 protein - 140 mM 10 mM Ca 0,0001 mM 2
mM
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Membrane potential - Goldman equation
A magnitude is determined by concentrations
permeabilities of membrane for potasium,
chlorine and sodium
P K , P Na , P Cl- - permeabilities for K,
Na, Cl- K, Na, Cl- - concentrations
100 4 45
Resting membrane potential for neuron - about
-70 mV
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?
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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
depolarizations or hyperpolarizations -
electricity - chemicals - generator potential
(sensory) - synaptic EPSP
(depolarization) IPSP (hyperpolarization)
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Neuronal recording
Rest 1
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SYNAPSE

• neurons signal to each other or to muscles or
  glands
• Electrical
• synapses
• electric signal
• goes 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

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Axo-dendritic synapses
Synapses - axo-dendritic - axo-somatic -
axo-axonal
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neuron
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Synaptic transmission

• Action potential comes via axon to the terminal
  at pre-synaptic membrane
• depolarization opens voltage gated Ca channels -
  Ca diffuse into neuron
• Ca inside - vesicles towards the membrane
  (proteins stenine and neurine) - exocytosis
  release of neurotransmitter (mediator) in the
  synaptic cleft

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• 3. diffusion of mediator molecules through the
  cleft (30-50 nm)
• 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)
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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
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• Neurotransmitters chemically aminoacids
  (glutamate, GABA, aspartate, glycine), peptides
  (vasopresin, somatostatine, neurotensine,...), m
  onoamines (norepinephrine, serotonine,
  acetylcholine,...)
• Excitatory
• - acetylcholine
• (neuromuscular junction)-
  glutamateInhibitory
• - GABA
• - glycine (spinal reflexes)
• excitation inhibition mostly
• determined by receptor
• In the brain are essential
• glutamate and GABA

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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?
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Summation of postsynaptic potentials (stimulation
of several synapses with ligand gated ion
channels)
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EPSP excitatory post-synaptic potential that
depolarize IPSP inhibitory post-synaptic
potential that 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
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SUMMATION of PSPs

• 1 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
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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
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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
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action potential arises at trigger zone initial
segment if the depolarization there reaches the
threshold
dendrites
axon with an axon collateral
soma
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Rest 3
I recommend to search GOOGLE summation of
postsynaptic potentials at the axon
hillock Animation 5.2 - Summation of Postsynaptic
Potentials and see the following http//sites.sin
auer.com/neuroscience5e/animations05.02.html S
uggestions what is important and how to remember
that important are appreciated, arent they?
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ACTION POTENTIAL
rising phase depolarization
falling phase repolarization
stimulation
hyperpolarization
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).
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500 times Na permeability At rest permeabilites
for K Na Cl- 100 4 45 At spike
depolarization 100 2000 45

• - Local (graded) depolarization to the threshold
  - firing level -
• Na channels open
• (voltage gated)
• - Na influx -
• rapid depolarization
• - SPIKE
• - even transpolarization
• positive charge at internal
• side of membrane for
• a short moment (and
• negative outside) -
• Na channels close
• (voltage gated) and
• K channels open (voltage
• gated)
• Na influx STOP K efflux -
• rapid repolarization

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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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1 action potential requires high, but limited
number of ions - considering the 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)

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exp insp
Rest 4

• airway pressure

diaphragm EMG
expiratory neuron
expiratory neuron burst
extracellular spike waveform
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Propagation of action potential
Local current spread (electrotonic conduction)
depolarization of nearby part of membrane
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Propagation of action potential local currents
refractoriness
- 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
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Saltatory conduction
from one node of Ranvier to the next one
orthodromicconduction
antidromicconduction
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Electrical stimulation of nerve (muscle) 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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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

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• 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.