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The Physiology of a

Neuron
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
soma Ranvier

axon hillock Schwann cell


initial segment
myelin sheath
nucleus
Propagation of neuronal excitation from
dendrites to the axon

dendrites
soma

axon with an
axon collateral
Cell/Plasma Membrane - reminder
double-layer of phospholipid + cholesterol + proteins
Role of Ion Channels
Types of plasma membrane ion channels:

Passive or leakage channels – always open


Chemically gated channels – open with binding of a
specific neurotransmitter
Voltage-gated channels – open and close in response to
a membrane potential (change in charge)
Mechanically gated channels – open and close in
response to physical deformation of receptors
Ion Channels

• Special proteins in the plasma


membrane that allow specific
ions to pass through.

• Some remain open all the time.


Others will open and close
depending on the conditions of
the cell and its environment.
Operation of chemical Gated
Channel

Figure 11.6a
Operation of a Voltage-Gated
Channel

Figure 11.6b
Gated Channels
When gated channels are open:

Ions move along chemical gradients, diffusion from


high concentration to low concentration.

Ions move along electrical gradients, towards the


opposite charge.
Together they are called the Electrochemical
Gradient
An electrical current and voltage changes are created
across the membrane
Electrochemical Gradient
The Electrochemical Gradient is the foundation of all
electrical phenomena in neurons.

It is also what starts the Action Potential.


Resting Membrane Potential

• Is the difference in electrical charge on the outside and


inside of the plasma membrane in a resting neuron (not
conducting a nerve impulse).

• The outside has a positive charge and the inside has a


negative charge.

• We refer to this as a polarized membrane.

• A resting neuron is at about -70mV


RESTING MEMBRANE
POTENTIAL
• Resting Membrane Potential (RMP) is the
voltage (charge) difference across the cell
membrane when the cell is at rest.
• In neurons, the resting membrane potential is
usually about –70 mV, which is close to the
equilibrium potential for K+.
• Because there are more open K+ channels
than Na + channels at rest, the membrane
permeability to K+ is greater.
A membrane potential results from separation of positive
and negative charges across the cell membrane.
RESTING MEMBRANE
POTENTIAL
RESTING MEMBRANE
POTENTIAL
RESTING MEMBRANE
POTENTIAL
ELECTROCHEMICAL
GRADIENT
POLARIZED
UNIVERSE = BALANCE
CHEMICALLY-GATED
CHANNEL
Resting Membrane Potential (Vr)
•The potential difference (–70 mV) across the membrane of a
resting neuron

•It is generated by different concentrations of Na+, K+, Cl,


and protein anions (A)

•The cytoplasm inside a cell is negative and the outside of


the cell is positive. (Polarized)
Changes in Membrane Potential

•Changes are caused by three events


•Depolarization – the inside of the membrane becomes
less negative

•Repolarization – the membrane returns to its resting


membrane potential

•Hyperpolarization – the inside of the membrane


becomes more negative than the resting potential
Changes in Membrane Potential

Figure 11.9
Graded Potentials
•A stimuli from sensory input causes the gated ion channels
to open for a short period of time.

•Positive Cations flow into the cell and move towards


negative locations around the stimuli.

•Alternately the now negative area on the outside of the cell


will flow towards the positive areas.

•However, this spread of depolarization is short lived


because the lipid membrane is not a good conductor and is
very leaky, so charges quickly balance out.
Graded Potentials

Figure 11.10
Graded Potentials

Figure 11.11
What is an action
potential?
•The synchronized opening and closing of Na++
and K gates result in the movement of
+
electrical charges that generates a nerve
impulse or action potential.

•Action potentials reach the end of each


neuron where these electrical signals are either
transmitted directly to the next cell in the
sequence via gap junctions, or are responsible
for activating the release of specialized
neurotransmitter chemicals.
Action Potential
• A momentary change in electrical potential
associated with the passage of an impulse
along the membrane of a muscle cell or
nerve cell.
• An Action potential is the neurons way of
transporting electrical signals from one cell
to the next.
• Actionpotentials aretheprimary electricalresponses
of neurons and other excitable tissues, and they are
the main form of communication within the nervous
system.
• They areduetochanges in theconductionofions
across the cellmembrane.
• The electrical events in neurons are rapid, being
measured in milliseconds (ms) ; and the potential
changes aresmall,beingmeasured in millivolts
(mV).
The Nerve Impulse or Action
Potential
• Is the electrical current
moving from the dendrites to
cell body to axon.

• It results from the movement


of ions (charged particles)
into and out a neuron
through the plasma
membrane.
Action Potentials (APs)

•A brief change in membrane potential from -70mV


(resting) to +30mV (depolarization)

•Action potentials are only generated by muscle cells and


neurons

•They do not decrease in strength over distance


•An action potential in the axon of a neuron is a nerve
impulse
Action Potential: Step 2 Cont.
•Na+ will continue to rush in making the inside less and less
negative and actually overshoots the 0mV (balanced) mark
to about +30mV.
Feedback control in voltage-gated ion channels in
the membrane.
Na + channels exert positive feedback.
K + channels exert negative
feedback
How an action potential is
propagated?

• The action potential is propagated down the


length of the neuron, from its input source at
the dendrites, to the cell body, and then
down the axon to the synaptic terminals
Why is there a difference?

1. There is 30 times more K+ inside the cell than


outside and about 15 times more Na+ outside
than inside.
2. There are also large negatively charged
proteins trapped inside the cell. (This is why it
is negative inside.)
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
Why so much K+ inside?
• Special protein channels called sodium-potassium pumps
moving 3 Na+ out and bringing 2 K+ back in, when the
cell is at rest.

• In a resting cell there are no open channels for Na+ to


easily move back into the cell. However, there are some
K+ channels open at all time.

• Na+ causes the outside to be positive forcing more K+


into the cell. ( More potassium ions inside the resting
cell.)
Review

• In a resting neuron the inside of the cell has a


__________ charge.

• In a resting neuron potassium ions are in high


concentration __________ of the cell.

• The resting membrane potential of a neuron is about


_____mV.
How is a nerve impulse
generated?
Steps in an action potential

1. The neuron gets stimulated (ex. receives a signal from


another neuron). This stimulation causes a change in the
resting membrane potential (- 70 mV).

2. If a neuron is stimulated enough the inside of the cell will


reach a critical level called threshold (about - 55mV).

3. At this point sodium ion channels will open.


Depolarization

4. Sodium ions rush into the neuron because of diffusion forces


(high to low) and charge attraction (+ and -).

5. The charge inside the cell eventually reaches about +30 mV.
(Relative to the outside of the cell the inside is now positive and
the outside is negative.) At this point the sodium ion channels
close.

• This change in polarization (- inside to +) is called depolarization


(step 4 and 5)
Repolarization

6. Next, potassium ion channels open up. This causes K+ to


rush out of the cell.

7. As the K+ leaves it causes the inside of the cell to


become negative again (-70mV). This is referred to as
repolarization (step 6 and 7).
rising phase
depolarization

ACTION POTENTIAL
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).
- Local (graded) depolarization to 500 times Na permeability
the threshold - firing level - At rest permeability- K+ : Na+ : Cl- 100 : 4 : 45
Na channels open At spike depolarization- K+: Na+ :Cl- 100 : 2000 : 45
(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
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 - 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)
Review

• What happens during the depolarization phase of an


action potential?

• What happens during the repolarization phase of an


action potential?
All-or-None Principle

• If a stimulus is strong
enough to generate an
action potential (reaches
threshold), the impulse is
conducted along the entire
length of the neuron at the
same strength.
ALL-OR-NONE ACTION
POTENTIALS
• The all-or-none law is the principle that the
strength by which a nerve or muscle fiber
responds to a stimulus is independent of
the strength of the stimulus.
• If that stimulus exceeds the
threshold potential, the nerve or muscle
fiber will give a complete response;
otherwise, there is no response.
Continuous Conduction

• Occurs in unmyelinated neurons.

• It is a step-by-step depolarization
of each adjacent area of the axon
(or dendrite) membrane.

• It results form one area


depolarizing causing the next area
to reach threshold and
depolarize.
Saltatory Conduction

• Occurs in myelinated neurons.

• Depolarization only occurs at the nodes of


Ranvier.
• The action potential jumps from one node to the
next.

• Saltatory conduction will conduct the signal much


faster than continuous conduction.
Saltatory Conduction

•Current passes through a myelinated axon only at the


nodes of Ranvier

•Voltage-gated Na+ channels are concentrated at these


nodes and Action potentials jump from one node to the
next

•Much faster than conduction along unmyelinated axons


where the entire axon has continuous conduction.
Saltatory Conduction

Figure 11.16
Saltatory
conduction

from one node of Ranvier to the


next one

orthodromic
conduction

antidromic
conduction
ORTHODROMIC &
ANTIDROMIC CONDUCTION
• An axon can conduct in either direction.
• When an action potential is initiated in the middle of
the axon, two impulses traveling in opposite directions
are set up by electrotonic depolarization on either side
of the initial current sink.
• In the natural situation, impulses pass in one direction
only, ie, from synaptic junctions or receptors along
axons to their termination.
• Such conduction is called orthodromic conduction.
Conduction in the opposite direction is called
antidromic conduction.
The SYNAPSE
•This is the region where communication
occurs between 2 neurons or between a
neuron and a target cell
•A neurotransmitter is released from the
nerve cell towards the other cell with
receptor
What is synaptic transmission?

•Synaptic transmission is the process by which nerve


cells communicate among themselves and with
muscles and glands.

•The synapse is the anatomic site where this


communication occurs.

•Most synaptic transmission is carried out by a


chemical called a neurotransmitter.
The neurotransmitter is manufactured
by the neuron and stored in vesicles at
the axon terminals
When the action potential reaches the axon
terminal, it causes the vesicles to release the
neurotransmitter molecules into the synaptic cleft.
The neurotransmitter diffuses across the cleft
and binds to receptors on the post-synaptic cleft
cell.
Then the activated receptors cause changes in
the activity of the post-synaptic neuron.
The neurotransmitter molecules are
released from the receptors and diffuse
back into the synaptic cleft.
The neurotransmitter is reabsorbed by the
pre synaptic neuron. This process is known

as reuptake. STOP
Neurotransmitters
neuron
Synaptic
transmission

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

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