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Nerve Physiology
• Morphology:
 Dendrites: The neural cells have five to seven process called dendrites that extended outward from the cell body
and arborize ‫تتفرع‬extensively.
 Axon: It is fibrous structure that originates from a somewhat thickened area of the cell body (the axon hillock).
 Synaptic knobs: The axon divides into terminal branches, each ending in a number of synaptic knobs. The knobs
are also called (terminal buttons or axon telodendria).They contain granules or vesicles in which the synaptic
transmitters secreted by the nerve are stored.
Schwann cell:
The axons of many neurons are myelinated (i.e. they acquire a sheath of myeline, a protein-lipid complex that is
warped around the axon). Outside the CNS, the myelin is produced by Schwann cells, found along the axon. Myeline
forms when a Schwann cell warps its membrane around an axon up to 100 times.
The myeline sheath envelops the axon except at its ending and at the nodes of Ranvier (periodic 1-μm constrictions
that are about 1 mm apart). Some of neurons are not myelinated (un-myelinated neurons) i.e. are simply surrounded
by Schwann cells without the warping of the Schwann cell membrane around the axon that produces myelin.
In CNS most neurons are myelinated, but the cells that form the myelin are oligodendrogliocytes rather than Schwann
cells.
In multiple sclerosis, a crippling autoimmune disease, there is patchy destruction of myeline in the CNS. The loss of
myeline is associated with delayed or blocked conduction in the de-myelinated axons.
Protein synthesis and axo-plasmic transport:
•
•
•
Nerve cells are secretory cells, but they differ from other secretory cells in that the secretory zone is generally at
the end of the axon, far removed from the cell body (soma).
All necessary proteins are synthesized in the cell body and then transported along the axon to the synaptic knobs
by the process of (axo-plasmic flow).
The cell body maintains the functional and anatomical integrity ‫سالمة‬of the axon: if the axon is cut, the part distal
to the cut degenerates (wallerian degeneration).
Membrane potential:
Membrane potential (also trans-membrane potential or membrane voltage)
Membrane potential is the difference in electrical potential between the interior and the exterior of a
biological cell.
The membrane potential has two basic functions.
First, it allows a cell to function as a battery, providing power to operate a variety of "molecular
devices" embedded in the membrane.
Second, in electrically excitable cells such as neurons and muscle cells, it is used for transmitting
signals between different parts of a cell.
Membrane potential is a separation of opposite charge across the plasma membrane
Membrane potential is a difference in the relative number of cations (+ ions) and anions (-ions) in the ICF
and ECE.
Membrane potential is separation of opposite charges across the membrane. Work must be performed
(energy expended) to separate opposite charges after they have come together.
Membrane potential is measured in units of volts or milli-volt.
The vast majority of the fluid in the ECF and ICF is electrically neutral. The unbalanced charges accumulate
in the thin layer along the plasma membrane (These separated charges represent only a small fraction of
the total number of charged particles (ions) present in the ICF and ECF).
Membrane B has more potential than membrane A and less potential than membrane C
The magnitude of the potential depends on the degree of separation of the opposite charges
The term membrane potential refers to the difference in charge between the water-thin
regions of ICF and ECF lying next to the inside and outside of the membrane, respectively.
• Membrane potential is due to difference in the concentration and permeability of key ions
• All cells have membrane potential.
• The cells of excitable tissues (e.g. nerve cells and muscle cells) have the ability to produce rapid, transient
changes in their membrane potential when excited (electrical signals or action potential).
• The constant membrane potential present in the cells of non-excitable tissues (cells do not produce action
potential most of the cells in the body are non-excitable) and those of excitable tissues when they are at
rest (i.e. when they are not producing electrical signals) known as the resting membrane potential.
• In the body, electrical charges are carried by ions. The ions primarily responsible for the generation of the
resting membrane potential are Na+, K+, and A- (The last refers to the large, negatively charged (anionic)
intracellular proteins). Other ions (calcium, chloride, and bicarbonate, to name a few) do not make a direct
contribution to the resting electrical properties of the plasma membrane in most cells, even though they
play other important roles in the body
• Note
• Na+ is in greater concentration in the extracellular fluid and K+ is in much higher concentration in the
intracellular fluid.
• Na inside /Na outside = 0.1; K inside /K outside = 30.0
Factors affecting membrane potential
1. Effects of Na –K pump on membrane potential:
 About 20% of the membrane potential is directly generated by the Na+-K+ pump. ( three Na+ out for every two K+ it transports
in).
The remaining 80% is caused by the passive diffusion of K+ and Na+ down concentration gradients.
2. Effects of the movements of K alone on membrane potential: K equilibrium potential:
The concentration gradient for K+ would tend to move this ion out of the cell), they would carry their positive charge with them, so
more positive charges would be on the outside (this is called diffusion equilibrium).
Diffusion potential:
• A diffusion potential is the potential difference generated across a membrane
because of a concentration difference of an ion
• The size of the diffusion potential depends on the size of the concentration
gradient.
•A diffusion potential can be generated only if the membrane is permeable to the
ion.
• The sign of the diffusion potential depends on whether the diffusing ion is
positively or negatively charged.
• Diffusion potentials are created by the diffusion of very few ions and, therefore,
do not result in changes in concentration of the diffusing ions.
Negative charges in the form of A~ would be left behind on the inside (Remember
that the large protein anions cannot diffuse out, despite a tremendous
concentration gradient.) A membrane potential would now exist.
Equilibrium potential:
• The equilibrium potential is the diffusion potential that exactly balances (opposes) the tendency for
diffusion caused by a concentration difference. At electrochemical equilibrium, the chemical and electrical
driving forces that act on an ion are equal and opposite, and no more net diffusion of the ion occurs.
The equilibrium potential will be reached when there is equal amounts of K+ ions on both sides of
the cell membrane ()‫مالحضة مهمة‬
The membrane potential at potassium equilibrium potential (EK+) is -90 mV. By convention, the sign always
designates the polarity of the excess charge on the inside of the membrane. A membrane potential of
-90 mV means that the potential is of a magnitude of 90 mV, with the inside being negative relative to the
outside. A potential of +90 mV would have the same strength, but in this case the inside would be more
positive than the outside.
3. Effects of the movements of Na alone on membrane potential: Na equilibrium potential:
The Na+ equilibrium potential (ENa+)
would be + 60 mV.
Membrane potentials in cells are determined primarily by three factors:
1) The concentration of ions on the inside and outside of the cell;
2) The permeability of the cell membrane to those ions (i.e., ion
conductance) through specific ion channels;
3) The activity of electro-genic pumps (e.g., Na+/K+ ATPase) that
maintain the ion concentrations across the membrane.
Concurrent Potassium and sodium effects on membrane potential
The resting potential (-70 mV) is much closer to EK+ (-90mV) than to ENa+ (+60Mv)
K+ exerts the dominant effect on the resting membrane potential because
The membrane is more permeable to K+
The membrane at rest is 100 times more permeable to K+ than to Na+ because
typically the membrane has many more channels open for passive K + traffic than for
passive Na + traffic across the membrane.
The greater the permeability of the plasma membrane for a given ion, the greater
the tendency for that ion to drive the membrane potential toward the ion's own
equilibrium potential.
 The concentration gradients that exist across the plasma membrane
The ratios of these two respective ions from the inside to the outside are:
Na inside /Na outside = 0.1; K inside /K outside = 35.0
Using the Nernst equation to calculate equilibrium potentials
a. The Nernst equation is used to calculate the equilibrium potential at a given concentration
difference of a permeable ion across a cell membrane. It tells us what potential would exactly
balance the tendency for diffusion down the concentration gradient; in other words, at what
potential would the ion be at electro-chemical equilibrium?
E: Equilibrium potential, R: Gas constant, T: Temperature (in Kalven), z: ion charge, F:
Faraday's constant.
Ci: Intra-cellular ion concentration (mM), Ce: Extra-cellular ion concentration (mM).
But:
Then the final equation will be:
‫بتعويض المعادلة‬: ‫مالحضة‬
Hypokalemia leads to hyperpolraized resting membrane potential (-90 instead of -70 mV)
Hyperkalemia leads to decrease resting membrane potential (-60 instead of -70 mV)
Hypernatremia or increased levels of plasma sodium will lead to a rise in resting membrane potential (it
will shift towards the positive side (-60 instead of -70 mV)). Therefore action potentials are triggered off
more easily,
In hyponatremia or decreased levels of plasma sodium, the opposite will happen because resting
membrane potential becomes more negative- threshold potential increases and frequency of action
potentials will decrease
The Goldman Equation Is Used to Calculate the Diffusion Potential When the Membrane Is
Permeable to Several Different Ions.
Note: Nernst equation to calculate equilibrium potentials and Goldman Equation Is Used to Calculate the
Diffusion Potential
When a membrane is permeable to several different ions, the diffusion potential that develops depends on
three factors:
(1) the polarity of the electrical charge of each ion,
(2) the permeability of the membrane (P) to each ion, and
(3) the concentrations (C) of the respective ions on the inside (i) and outside (o) of the membrane, and (P) is
the permeability.
Thus, the following formula, called the Goldman equation or the Goldman-Hodgkin-Katz equation, gives the
calculated membrane potential on the inside of the membrane when two univalent positive ions, sodium
(Na+) and potassium (K+), and one univalent negative ion, chloride (Cl−), are involved.
Where (V: mv) is membrane potential; P: Permeability; i: concentration in; o: concentration out
Several key points become evident from the Goldman equation.
First, sodium, potassium, and chloride ions are the most important ions involved in the development of
membrane potentials in nerve and muscle fibers, as well as in the neuronal cells in the nervous system. The
concentration gradient of each of these ions across the membrane helps determine the voltage of the
membrane potential.
Second, the quantitative importance of each of the ions in determining the voltage is proportional to the
membrane permeability for that particular ion. That is, if the membrane has zero permeability to potassium
and chloride ions, the membrane potential becomes entirely dominated by the concentration gradient of
sodium ions alone, and the resulting potential will be equal to the Nernst potential for sodium. The same
holds for each of the other two ions if the membrane should become selectively permeable for either one of
them alone.
Third, a positive ion concentration gradient from inside the membrane to the outside causes
electronegativity inside the membrane. The reason for this phenomenon is that excess positive ions diffuse
to the outside when their concentration is higher inside than outside.
The diffusion carries positive charges to the outside; but leaves the non-diffusible negative anions on the
inside, thus creating electro-negativity on the inside ‫داخل يصبح سالب امابخروج موجب اودخول سالب‬
The opposite effect occurs when there is a gradient for a negative ion. That is, a chloride ion gradient from
the outside to the inside causes negativity inside the cell because excess negatively charged chloride ions
diffuse to the inside, while leaving the non-diffusible positive ions on the outside.
Fourth, as explained later, the permeability of the sodium and potassium channels undergoes rapid
changes during transmission of a nerve impulse, whereas the permeability of the chloride channels does not
change greatly during this process. Therefore, rapid changes in sodium and potassium permeability are
primarily responsible for signal transmission in neurons
• Excitation and conduction in neurons:
o Nerve cells have low threshold for excitation.
o The stimulus to nerve may be electrical, chemical or mechanical.
o Two types of physiochemical distribution are produced:
1.Electro-tonic potential or graded potential or local, non-propagated potential
depending on their location, (synaptic or electro-tonic potential: resulting
from a local change in ionic conductance).
2.Action potential or Propagated potential, (or nerve impulses).
o They are due to changes in the conduction of ions across the cell membrane.
o The impulse is normally conducted along the axon to its termination.
Grading potential (local potential):
Graded potentials are
 local changes in membrane potential that
 occur in varying grades or degrees of magnitude or strength.
For example, membrane potential could change from -70 mV to -60 mV (a 10-mV graded
potential). But it will never reaches the threshold otherwise it will be propagated
The stronger a triggering event, the larger the resultant graded potential:
1. The stronger the triggering event
▼
the more gated channels that open
▼
the greater the positive charge entering the cell
▼
the larger the depolarizing graded potential at the point of origin.
2. The longer the duration of the triggering event
▼
the longer the duration of the graded potential.
Graded potentials spread by passive current flow:
When a graded potential occurs locally in a nerve or muscle cell membrane, the remainder of
the membrane is still at resting potential.
The temporarily depolarized region is called an active area.
Inside the cell, the active area is relatively more positive than the neighboring inactive areas
that are still at resting potential.
Outside the cell, the active area is relatively less positive than these adjacent areas.
▼
Because of this difference in potential; electrical charges, in this case carried by ions, passively
flow between the active and adjacent resting regions on both the inside and outside of the
membrane
Any flow of electrical charges is called a current. By convention, the direction of current flow is
always designated by the direction in which the positive charges are moving (i.e. inside the
cell and not outside the cell as seen in Figure C).
In this manner, current spreads in both directions away from the initial site of the potential
change.
.
Graded potentials die out over short distance (decrement fashion):
Current is lost across the plasma membrane as charge-carrying ions leak through the "uninsulated" parts of the membrane, that is, through open channels. Because of this current
loss, the magnitude of the local current progressively diminishes with increasing distance
from the initial site of origin. Thus the magnitude of the graded potential continues to
decrease the farther it moves away from the initial active area. Another way of saying this is
that the spread of a graded potential is decrement (gradually decreases)
Although graded potentials have limited signaling distance, they are critically important to the
body's function. The following are all graded potentials: postsynaptic potentials, receptor
potentials, end-plate potentials, pacemaker potentials, and slow-wave potentials.
The amount of current that flows between two areas depends
1.The difference in potential between the areas. The greater the
difference in potential, the greater the current flow.
2.The strength of stimuli: the stronger the strength, the greater the
current flow.
3.Local potential: Local potential produced in response to several stimuli
is larger than one produced from a single stimuli.
4.The resistance of the material through which the charges are moving.
Resistance is the hindrance to electrical charge movement. The lower
the resistance, the greater the current flow.
Conductors have low resistance, providing little hindrance to current flow.
The current does not flow across the plasma membrane's lipid bi-layer.
Current, carried by ions, can move across the membrane only through
ion channels.
Resting membrane potential:
When two electrodes are connected through a suitable amplifier to a Cathode ray oscilloscope and placed
on the surface of single axon, no potential difference is observed. However, if one electrode is inserted into
the interior of the cell, a constant potential difference is observed, with the inside negative relative to outside
of the cell at rest. The resting membrane potential is found in almost all cells. In neurons, it is usually about
-70 mV.
Resting (Cell at rest), membrane (on two side of the cell membrane), potential (voltage difference)
-70 mV (inside the cell is less than outside the cell by 70 mV)
The transfer of an incredibly small number of ions through the membrane can establish the normal “resting
potential” of −70 millivolts inside the nerve fiber, which means that only about 1/3,000,000 to 1/100,000,000
of the total positive charges inside the fiber must be transferred. Also, an equally small number of positive
ions moving from outside to inside the fiber can reverse the potential from −70 millivolts to as much as +35
millivolts within as little as 1/10,000 of a second. Rapid shifting of ions in this manner causes the nerve
signals.
Action potential:
Action potential event
The first manifestation of the approaching action potential is a beginning depolarization of the membrane. After an initial 15 mV of
depolarization, the rate of depolarization increases. The point at which this change in rate occurs is called the firing level or the
threshold (-55mV). Therefore, the tracing on the oscilloscope rapidly reaches and overshoots the iso-potential (zero potential)
line to an approximately +35mV.
It is then reverses and falls rapidly toward the resting level. When re-polarization is about 70% completed, the rate of repolarization decreases and the tracing approaches the resting level more slowly. The sharp rises and rapidly fall are the spike
potential of the axon, and the slower fall at the end of the process is the after-depolarization (about 4ms). After reaching the
previous resting level, the tracing overshoots slightly in hyper-polarization direction to form the small but prolonged after-hyperpolarization (the period that persists until the membrane potassium permeability returns to its usual value). When recorded with
one electrode in the cell, the action potential is called mono-phasic, because it is primarily in one direction. After-hyper-polarization
is about 1 to 2 mV in amplitude and lasts about 40 ms
a. De-polarization (or upstroke) makes the membrane potential less negative (the cell interior becomes less
negative).
b. Re-polarization (or down stroke) the return of cell membrane potential to resting potential after
depolarization.
c. Hyper-polarization (or under stroke) makes the membrane potential more negative (the cell interior
becomes more negative).
d. Inward current is the flow of positive charge into the cell. Inward current depolarizes the membrane
potential.
e. Outward current is the flow of positive charge out of the cell. Outward current hyper-polarizes the
membrane potential.
f. Action potential is a property of excitable cells (i.e., nerve, muscle) that consists of a rapid depolarization,
or upstroke, followed by re-polarization of the membrane potential.
3. Ionic basis of action potential:
a. Resting membrane potential
• is approximately -70 mV, cell negative.
• is the result of the high resting conductance to K+, which drives the membrane potential toward the K+
equilibrium potential.
• At rest, the Na+ channels are closed and Na+ conductance is low.
b. Upstroke (or depolarization) of the action potential
(1) Inward current depolarizes the membrane potential to threshold.
A negative current value (i.e., inward current) can reflect either the movement of positive ions (cations) into
the cell or negative ions (anions) out of the cell. ‫مما يتسبب ان يصبح داخل الخلية موجب اكثر‬
(2) Depolarization causes rapid opening of the activation gates of the Na+ channel, and the Na+
conductance of the membrane promptly increases.
(3) The Na+ conductance becomes higher than the K+ conductance, and the membrane potential is driven
toward (but does not quite reach) the Na+ equilibrium potential of +65 mV. Thus, the rapid depolarization
during the upstroke is caused by an inward Na+ current.
(4) The overshoot is the brief portion at the peak of the action potential when the membrane potential is
positive.
c. Down-stroke (or Re-polarization) of the action potential
(1) Depolarization also closes the inactivation gates of the Na+ channel (but more slowly than it opens the
activation gates). Closure of the inactivation gates results in closure of the Na+ channels, and the Na+
conductance returns toward zero.
(2) Depolarization slowly opens K+ channels and increases K+ conductance to even higher levels than at
rest.
(3) The combined effect of closing the Na+ channels and greater opening of the K+ channels makes the K+
conductance higher than the Na+ conductance, and the membrane potential is re-polarized. Thus, repolarization is caused by an outward K+ current.
d. Undershoot (hyperpolarizing after potential)
• The K+ conductance remains higher than at rest for some time after closure of the Na+ channels. During
this period, the membrane potential is driven very close to the K+ equilibrium potential.
d. Undershoot (hyperpolarizing after potential)
• The K+ conductance remains higher than at rest for some time after closure of the Na+ channels. During
this period, the membrane potential is driven very close to the K+ equilibrium potential
Activation and Inactivation of the Voltage Gated Sodium Channel
The voltage-gated sodium channel in three separate states
A. Resting membrane potential (at -70mV):
Closed but capable of opening
Activation gate is closed
Inactivation gate is opened
No Na passes
B. Depolarization (from – 50mV to+35mV)
This means that the highest number of
Na is opened at threshold potential
(means highest number of Na ions)
and as we approaches the +35mV
the number decrease but when we
reaches +35mV no Na channel opened
(means no further Na ions enters)
Open, or activated
Activation gate is opened
Inactivation gate is opened
Na passes
C. Repolarization (from +30mV to-70mV)
Closed and not capable of opening
Activation gate is opened
Inactivation gate is closed
No Na passes
The sodium channel inactivation process is that the inactivation gate will not re-open until the membrane potential
returns to or near the original resting membrane potential level. Therefore, it is usually not possible for the sodium
channels to open again without first repolarization the nerve fiber.
Voltage Gated Potassium Channel and Its Activation
During the resting state, the gate of the potassium channel is closed and potassium ions are
prevented from passing through this channel to the exterior.
When the membrane potential rises from −70 millivolts toward zero, this voltage change
causes a conformational opening of the gate and allows increased potassium diffusion
outward through the channel. However,
because of the slight delay in opening
of the potassium channels, for the most part,
they open just at the same time that the
sodium channels are beginning to close
because of inactivation. Thus, the decrease
in sodium entry to the cell and the simultaneous
increase in potassium exit from the cell
combine to speed the repolarization
process, leading to full recovery of
the resting membrane potential within
another few 10,000ths of a second.
Re-establishing Sodium and Potassium ionic grading after action potentials are completed
(importance of energy metabolism)
1. For a single action potential, the energy expenditure for Na+-K+ pump is so minute that it cannot be
measured. Indeed, 100,000 to 50 million impulses can be transmitted by large nerve fibers before the
concentration differences reach the point that action potential conduction ceases.
2. A special feature of the Na+-K+ATPase pump is that its degree of activity is strongly stimulated when
excess sodium ions accumulate inside the cell membrane. In fact, the pumping activity increases
approximately in proportion to the third power of this intracellular sodium concentration. That is, as the
internal sodium concentration rises from 10 to 20 mEq/L, the activity of the pump does not merely double
but increases about eightfold. Therefore, it is easy to understand how the “recharging” process of the nerve
fiber can be set rapidly into motion whenever the concentration differences of sodium and potassium ions
across the membrane begin to “run down.”
3. The nerve fiber produces excess heat during recharging, which is a measure of energy expenditure when
the nerve impulse frequency increases.
General characteristics of nerve:
1. ALL-or-none Law:
Threshold potential (Threshold intensity): It is the minimal intensity of stimulating current that,
acting for a given duration, will just produce an action potential is the membrane potential at
which the action potential is inevitable ‫ال مفرر مهر‬. At threshold potential, net inward current
becomes larger than net outward current.
Electronic potentials(grade potential): Although sub-threshold stimuli do not produce an
action potential, they do have an effect on the membrane potential.
If net inward current is less than net outward current, no action potential will occur (i.e., all-ornone response
All-or-none law: 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.
Further increase in the intensity of a stimulus (Supra-threshold stimulus) produces no increment
or other change in the action potential as long as the other experimental condition remains constant.
The action potential fails to occur if the stimulus is sub-threshold in magnitude,
and it occurs with constant
amplitude and form regardless of the
strength of the stimulus if the stimulus is
at or above the threshold intensity.
The above account deals with the
response of a single nerve fiber. If a nerve
trunk is stimulated, then as the exciting stimulus
is progressively increased above threshold, a
larger number of fibers respond. The minimal
effective (i.e., threshold) stimulus is adequate
only for fibers of high excitability, but a stronger
stimulus excites all the nerve fibers. Increasing
the stimulus further does increase the response
of whole nerve
2. Propagation of action potentials
 The conduction is an active, self-propagating process, and the impulse moves
along the nerve at a constant amplitude and velocity.
 The electrical events in neurons are rapid, being measured in milli-seconds (ms), and the
potential changes are small, being measured in milli-volts (mV).
Propagation occurs by the spread of local currents to adjacent areas of membrane, which
are then depolarized to threshold and generate action potentials.
Conduction velocity is increased by:
a. increase fiber size. Increasing the
diameter of a nerve fiber results in
decreased internal resistance; thus,
conduction velocity down the nerve
is faster.
b. Myelination.
Myelin acts as an insulator around nerve axons and increases conduction velocity.
Depolarization in myelinated axons jumps from one node of Ranvier to the next this is called (saltatory
conduction).
Because the cytoplasm of the axon is electrically conductive and because the myelin inhibits charge leakage
through the membrane depolarization at one node of Ranvier is sufficient to elevate the voltage at a neighboring
node to the threshold for action potential initiation. Thus in myelinated axons, action potentials do not propagate
as waves, but recur ‫تكررر‬at successive nodes and in effect "hop" ‫قفر‬along the axon, by which process they travel
faster up to 50 times faster than the fast un-myelinated fibers. Action potential in unmylinated axon occurs over
the entire of the axon membrane
The spatial distribution of ion channels along the axon plays a key role in the initiation and regulation of the
action potential. Voltage-gated Na+ channels are highly concentrated in the nodes of Ranvier and the initial
segment in myelinated neurons.
The number of Na channel per square
micro-meter of membrane in myelinated
mammalian neurons has been estimated
to be 2000-12,000 at the nodes of Ranvier.
Along the axon of un-myelinated neurons,
the number is about 110 In many myelinated
number neurons, the Na channels are
flanked ‫يحيط‬by K channels that are involved in
re-polarization.
In summary, the charge will passively
depolarize the adjacent node of Ranvier
to threshold, triggering an action potential
in this region and subsequently depolarizing the
next node, and so on.
3. Stereotypical size and shape
Each normal action potential for a given cell type look identical, depolarizes to the same potential, and repolarizes
back to the same resting potential
4. Refractory ‫مقاوم‬periods
a. Absolute refractory period
• is the period during which another action potential cannot be elicited, no matter how large the stimulus.
• coincides ‫يتزامن‬with almost the entire duration of the action potential.
• Explanation: Recall ‫تذكر‬that the inactivation gates of the Na+ channel are closed when the membrane potential is
depolarized. They remain closed until re-polarization occurs. No action potential can occur until the inactivation gates
open.
b. Relative refractory period
• begins at the end of the absolute refractory period and
continues until the membrane potential returns to the
resting level.
• An action potential can be elicited ‫يضهر‬during this period
only if a larger than usual inward current is provided.
• Explanation: The K+ conductance is higher than at rest,
and the membrane potential is closer to the K+ equilibrium
potential and, therefore, farther from threshold; more inward
current is required to bring the membrane to threshold.
Ortho-dromic and anti-dromic conduction: An axon can conduct in either direction. When an
action potential is initiated in the middle of it, two impulses traveling in opposite directions are
set up by electro-tonic depolarization on either side of the initial current sink.
In a living animal, impulses normally pass in one direction only, i.e. from synaptic junction or receptors along
axons to their termination. Such conduction is called” ortho-dromic “. Conduction in the opposite direction is
called “anti-dromic”. Since synapses, unlike axons, permit conduction in one direction only, any anti-dromic
impulses that are set up fail to pass the first synapses they encounter and die out at that point
Nerve accommodation
The ability of nerve tissue to adjust to a constant source and intensity of stimulation so that some change in either intensity or
duration of the stimulus is necessary to elicit a response beyond the initial reaction
Potassium is the most abundant intracellular cation and about 98% of the body's potassium is found inside cells, with the
remainder in the extracellular fluid including the blood.
Increased extracellular potassium levels result in depolarization of the membrane potentials of cells due to the increase in
the equilibrium potential of potassium. This depolarization opens some voltage-gated sodium channels, but also increases
the inactivation at the same time. Since depolarization due to concentration change is slow, it never generates an action potential
by itself; instead, it results in accommodation. Above a certain level of potassium the depolarization inactivates sodium channels,
opens potassium channels, thus the cells become refractory.
Hyperkalemia open gates of K membrane potential is closer to threshold (Nernst equation) inactivation gates on Na
accommodation muscle weakness