tha action potential of neuronal cells

1. BIOPHYSICS OF ACTION
POTENTIAL & SYNAPSE
Ivan Poliaček

2. 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 hillock
initial segment
node of
Ranvier
Schwann cell

3. Propagation of neuronal excitation from
dendrites to the axon
dendrites
soma
axon with an
axon collateral

4. Membrane potential,
membrane depolarization,
hyperpolarization

5. Cell membrane - reminder
• double-layer of phospholipide + cholesterol + proteins

6. 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

7. A magnitude is determined by concentrations & permeabilities
of membrane for potasium, chlorine and sodium
     
     e
Cl
.
P
i
Na
.
P
i
K
.
P
i
Cl
.
P
e
Na
.
P
e
K
.
P
ln
.
F
T
.
R
V
Cl
Na
K
Cl
Na
K
m 
















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

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

9. Neuronal
recording
Rest # 1

10. 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

11. Axo-dendritic
synapses
Synapses:
- axo-dendritic
- axo-somatic
- axo-axonal

13. neuron

14. 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

15. 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)

16. 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

17. 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 mostly
determined by receptor
In the brain are essential:
glutamate and GABA

18. 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?

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

20. 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

21. 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

22. 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

23. 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

24. action potential arises at trigger zone = initial segment if the
depolarization there reaches the threshold
dendrites
soma
axon with an
axon collateral

26. 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.sinauer.com/neuroscience5e/animations05.02.html
Suggestions what is important and how to remember that important are
appreciated, aren’t they?
Rest # 3

27. 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 phase
depolarization
falling phase
repolarization
hyperpolarization

28. - 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
500 times Na permeability
At rest permeabilites for K+ : Na+ : Cl-
100 : 4 : 45
At spike depolarization 100 : 2000 : 45

29. 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

30. 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)

32. airway pressure
diaphragm EMG
expiratory
neuron
exp
insp
expiratory neuron burst
extracellular
spike
waveform
Rest # 4

33. Propagation
of action
potential
Local current
spread
(electrotonic
conduction) –
depolarization
of nearby
part of
membrane

34. - 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

37. Saltatory
conduction
from one node of Ranvier to the
next one
orthodromic
conduction
antidromic
conduction

38. 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]

39. 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

40. 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.