2. What is Action Potential?
• Action potential can be defined as the brief sequence of changes
which occur in the resting membrane potential when stimulated by a
threshold stimulus.
• It is a property of excitable cells, such as nerve fibers, skeletal muscle
fibers.
• Each action potential begins with a sudden change from the normal
resting negative membrane potential to a positive potential and ends
with an almost equally rapid change back to the negative potential.
3.
4. Phases of Action Potential
Resting Stage:
• The resting stage is the resting membrane potential before the action
potential begins.
• Resting membrane potential (−70 mV) is due to distribution of more
cations outside the cell membrane and more anions inside the cell
membrane.
• The membrane is said to be “polarized” during this stage because of the
−70 millivolts negative membrane potential with reference to the
extracellular fluid.
• At this point, though Na+ is more in ECF, it cannot enter the cell due to the
impermeability of the membrane
5. Depolarization:
• When normal polarized state of −70 millivolts is neutralized by the
inflowing, positively charged sodium ions, with the potential rising
rapidly in the positive direction—a process called depolarization.
• Depolarization occurs when threshold stimulus is applied to the cell
membrane.
Repolarization:
• The rapid diffusion of potassium ions to the exterior reestablishes the
normal negative resting membrane potential, which is called
repolarization of the membrane.
• Decrease in Na+ influx and efflux of K+ causes net transfer of positive
charge out of the cell that serves to complete the repolarization
6. Hyperpolarization:
• The slow efflux of K+ continues even after the resting membrane
potential is reached, resulting in a prolonged phase of
hyperpolarization during which the membrane potential falls below
−70 mV. However, little after, the voltage-gated K+ channels also shut
down and membrane potential is brought to resting stage.
7. Threshold potential
• It is the membrane potential at which the action potential is
inevitable.
• This occurs when the number of sodium ions entering the fiber is
greater than the number of potassium ions leaving the fiber.
• Therefore, a sudden increase in the membrane potential in a nerve
fiber, from −70 millivolts up to about −55 millivolts, usually causes
the explosive development of an action potential.
8. Action potential occurs secondary to stimulus
• Any stimulus that is large enough to increase the membrane potential
from -70 millivolts to −55 millivolts (an increase of around 15 to 30
mV)is the threshold stimulation.
• Types of stimulus could be:
• Mechanical (Pressure, touch)
• Electrical stimulus (in laboratory settings)
• Chemical stimulus (Neurotransmitters)
• However some cells are self- excitable, such as cardiac muscle cells.
They depolarize spontaneously as they exhibit the property of
rhythmicity.
9. Ionic basis of Action potential
Voltage-Gated Sodium Channel:
• They are closed under normal resting conditions.
• They are extremely voltage sensitive. When the inside membrane potential reaches
threshold potential of – 55 mV, a conformational change occurs leading to opening of
their activation gates, and influx of sodium ions leading to depolarization.
• These are fast acting sodium channels. The same depolarization that open activation
gates, also closes the inactivation gates of the Na+ channels (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.
• Another important characteristic of the sodium channel inactivation process is that the
inactivation gate will not reopen until the membrane potential returns to the original
resting membrane potential level – This forms the basis of refractory period.
10. Voltage-Gated Potassium Channel:
• Depolarization slowly opens K+ channels about the same time that the Na+
channels are beginning to close because of inactivation.
• 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 repolarized.
• Thus repolarization is caused by an outward K+ current.
Hyperpolarizing afterpotential:
• The K+ conductance remains higher than at rest for sometime after closure
of the Na+ channels. During this period, the membrane potential becomes
more negative than the resting membrane potential (close to the K+
equilibrium potential).
• However, The final ionic distribution is brought to the resting state by the
action of Na+–K+ pump and the leak channels (K+ and Na+)
12. Propagation of Action Potential
• An action potential elicited at any one point on an excitable cell
membrane usually excites adjacent portions of the membrane, and
travels along the entire length of nerve fiber.
• Action potential travels in direction away from the stimulus.
• Once an action potential has been elicited at any point on the
membrane of a normal fiber, the depolarization process travels over
the entire membrane if conditions are right, but it does not travel at
all if conditions are not right. This principle is called the all or-nothing
principle.
13. Conduction velocity of Action Potential
Conduction velocity or velocity of propagation is increased by:
• Increased fiber size: Increasing the diameter of a nerve fiber results
in decreased internal resistance; thus, conduction velocity down the
nerve is faster.
• Myelination: Myelin acts as an insulator around nerve axons and
increases conduction velocity. Myelinated nerves exhibit saltatory
conduction because action potentials can be generated only at the
nodes of Ranvier, where there are gaps in the myelin sheath
14.
15. Absolute Refractory Period
• It is the period during which another action potential cannot be
elicited, no matter how large the stimulus.
• Coincides with almost the entire duration of the action potential.
• Recall that the inactivation gates of the Na+ channels are closed when
the membrane potential is depolarized. They remain closed until
repolarization occurs. No action potential can occur until the
inactivation gates open.
16. 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 during this period only if a larger
than usual inward current is provided.
• Reason: The K+ conductance is higher than at rest, and the
membrane potential is closer to the K+ equilibrium potential and,
therefore, farther from threshold (i.e. -55 mV); Therefore, more
inward current is required to bring the membrane to threshold.
19. Question Stem
The resting potential of a myelinated nerve fiber is primarily dependent
on the concentration gradient of which of the following ions?
• A) Ca+
• B) Cl −
• C) HCO3 −
• D) K+
• E) Na
20. Answer D
• The resting potential of any cell is dependent on the concentration
gradients of the permeant ions and their relative permeabilities
(Goldman equation). In the myelinated nerve fiber, as in most cells,
the resting membrane is predominantly permeable to K+ . The
negative membrane potential observed in most cells (including nerve
cells) is due primarily to the relatively high intracellular concentration
and high permeability of K+ .
21. Question Stem
The figure below shows the change in membrane potential during an action potential in a
giant nerve fiber. Refer to it when answering the next two questions.
22. Question 1
Which of the following is primarily responsible for the change in
membrane potential between points B and D?
• A) Inhibition of the Na+ , K+ -ATPase
• B) Movement of K+ into the cell
• C) Movement of K+ out of the cell
• D) Movement of Na+ into the cell
• E) Movement of Na+ out of the cell
23. Answer D
• At point B in this action potential, Vm has reached threshold
potential and has triggered the opening of voltage-gated Na+
channels. The resulting Na+ influx is responsible for the rapid, self-
perpetuating depolarization phase of the action potential.
24. Question 2
Which of the following is primarily responsible for the change in
membrane potential between points D and E?
• A) Inhibition of the Na+ , K+-ATPase
• B) Movement of K+ into the cell
• C) Movement of K+ out of the cell
• D) Movement of Na+ into the cell
• E) Movement of Na+ out of the cell
25. Answer C
• The rapid depolarization phase is terminated at Point D by the
inactivation of the voltage-gated Na+ channels and the opening of the
voltage-gated K+ channels. s. The latter results in the efflux of K+ from
the cytosol into the extracellular fluid and repolarization of the cell
membrane.
26. Question Stem
• During the course of a nerve action potential (shown), a 10-mV electrical stimulus
is delivered at the time indicated by the arrow. In response to the electrical
stimulus, a second action potential will:
27. • A) be identical to the first
• B) have a higher amplitude
• C) have a lower amplitude
• D) not occur
• E) have a slower velocity
• F) have a faster velocity
28. Answer D
• A new action potential cannot occur in an excitable fiber when the
membrane is still depolarized from the preceding action potential.
The reason for this restriction is that shortly after the action potential
is initiated, the sodium channels (or calcium channels, or both)
become inactivated, and no amount of excitatory signal applied to
these channels at this point will open the inactivation gates. The only
condition that will allow them to reopen is for the membrane
potential to return to or near the original resting membrane potential
level. Then, within another small fraction of a second, the inactivation
gates of the channels open and a new action potential can be
initiated.
29. Question Stem
A newly developed local anesthetic blocks Na+ channels in nerves.
Which of the following effects on the action potential would it be
expected to produce?
(A) Decrease the rate of rise of the upstroke of the action potential
(B) Shorten the absolute refractory period
(C) Abolish the hyperpolarizing afterpotential
(D) Increase the Na+ equilibrium potential
(E) Decrease the Na+ equilibrium potential
30. Answer A
• Blockade of the Na+ channels would prevent action potentials. The
upstroke of the action potential depends on the entry of Na+ into the
cell through these channels and therefore would also be reduced or
abolished.
• The absolute refractory period would be lengthened because it is
based on the availability of the Na+ channels.
• The hyperpolarizing afterpotential is related to increased K+
permeability. The Na+ equilibrium potential is calculated from the
Nernst equation and is the theoretical potential at electrochemical
equilibrium (and does not depend on whether the Na+ channels are
open or closed).
