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Presents to you by
A stimulus is an external force or event which when applied to
an excitable tissue produces a characteristic response.
Subthreshold stimulus:
A stimulus which is too weak to produce a response is called a
Subthreshold stimulus.
Threshold stimulus:
The minimum strength of stimulus that can produce excitation is
called a Threshold stimulus.
Suprathreshold stimulus:
Stimuli having strengths higher than threshold stimulus are
called Suprathreshold stimuli.
Channels and their
 Activation of Channels: Channel opening to allow ion flow is called
channel activation. For example, Na channels and K channels of
axons are both activated by cell depolarization. The Na channels
open very rapidly, but the K channels are slower to open. The result
is an initial flow of Na across the membrane, followed later by a
flow of K.
 Inactivation of Channels: Channel closing and blocking ion flow is
called Inactivation. This is similar to doors with an automatic open
close mechanism. The door opens when you hit the button, then
after a certain period of time, it closes itself, whether you are still
standing in the doorway or not. An inactivated channel returns to
its normal closed state shortly after the membrane repolarizes.
How voltage-gated channels
work ?
 Sodium voltage-gated
channels: are fast channels
& have 2 gates:
- An inner Activation
gate(closed in resting
- An outer
Inactivation gate(open in
resting state)
 Potassium channels: are
slow channels & have only
ONE gate.
 These channels are
different from Sodium &
Potassium leak channels.
 The Sodium-Potassium
PUMP is present
 When ion channels open, ions may move into or out of the cell.
 The direction of ion movement depends on the electrochemical
(combined chemical and electrical) gradient of the ion. Potassium
ions usually move out of the cell. Sodium, Chloride and Calcium
usually flow into the cell. The net flow of ions across the membrane
depolarizes or hyperpolarizes the cell, creating an electrical signal.
Continue ….
The resting membrane potential of living cells is determined primarily
by the K concentration gradient and the cells resting permeability to K,
Na, and Cl.
A change in either the K concentration gradient or ion permeabilities
changes the membrane potential. For example, at rest, the cell
membrane of a neuron is only slightly permeable to Na. However, if
the membrane suddenly increases its Na permeability, Na enters the
cell, moving down its electrochemical gradient. The addition of
positive Na to the intracellular fluid depolarizes the cell membrane
and creates an electrical signal. The movement of ions across the
membrane can also hyperpolarize a cell. If the cell membrane
suddenly becomes more permeable to K, positive charge is lost from
inside the cell and the cell becomes more negative (hyperpolarizes). A
cell may also hyperpolarize if negatively charged ions, such as Cl, enter
the cell from the extracellular fluid.
Basic concepts
 Polarization: Any time the value of the membrane potential is
other than 0 mV, in either the positive or negative direction,
the membrane is in a state of polarization.
 Depolarization: The membrane becomes less polarized; the
inside becomes less negative than at resting potential, with
the potential moving closer to 0 mV (e.g. a change from – 90
to – 80mv).
 Repolarization: The membrane returns to resting potential
after having been depolarized.
 Hyperpolarization: The membrane becomes more polarized;
the inside becomes more negative than at resting potential,
with the potential moving even farther from 0 mV (for
instance, a change from -90 to -100 mV).
Propagation of action potential
When the trace moves upward
(becomes less negative), the
potential difference between
the inside of the cell and the
outside (0 mV) decreases, and
the cell is said to have
depolarized. A return to the
resting membrane potential is
termed repolarization. If the
resting potential moves away
from 0 mV, the membrane
potential becomes more
negative, the potential
difference has increased, and
the cell has hyperpolarized.
 Would a cell with a resting
membrane potential of –
70 mV depolarize or
hyperpolarize in the
following cases? (You must
consider both the
concentration gradient and
the electrical gradient of
the ion to determine net
ion movement.)
(a) Cell becomes more
permeable to Ca2+.
(b) Cell becomes less
permeable to K+.
 Would the cell membrane
depolarize or hyperpolarize
if a small amount of Na+
leaked into the cell?
Action Potential:
An Action Potential is a self-propagating wave of electro-positivity that passes
along the surface of the nerve fibers from the cell body to the axon terminals.
 Duration: only 1 msec (same in all neurons).
 Also called: A Spike (because of its spike-like appearance).
 Action potentials serve as faithful, long-distance signals because they do not
diminish in size as they travel from site of initiation throughout the remainder
of the cell membrane
Think about the neuron that causes the muscle cells in your big toe to contract.
If you want to wiggle your big toe, commands are sent from your brain down
your spinal cord to initiate an action potential at the beginning of this neuron,
which is located in the spinal cord. The action potential travels all the way down
the neuron’s long axon, which runs through your leg to terminate on your bigtoe muscle cells. The signal does not weaken or die off , being instead preserved
at full strength from beginning to end.
How is the membrane potential, which is
usually maintained at a constant resting level,
altered to such an extent as to produce an
action potential?
During an action potential, marked changes in membrane permeability
to Na and K take place, permitting rapid fluxes of these ions down their
electrochemical gradients.
These ion movements carry the current responsible for the potential
changes that occur during an action potential.
A threshold or supra threshold stimulus when applied to the neuron
causes changes in the voltage that cause opening of the voltage-gated
sodium channels.
Action potentials take place as a result of the triggered opening and
subsequent closing of two specific types of channels: voltage-gated Na
channels and voltage-gated K channels.
How action potential generated?
Phases of an Action Potential
An Action Potential
has 3 phases:
Phase 1:
Phase 2:
Phase 3:
Phases of action potential
State of SODIUM channel gates:
 Resting state:
- Inactivation gates: OPEN
- Activation gates: CLOSED
 Depolarization:
- Activation gates: OPEN
- Inactivation gates: OPEN
 Peak:
- Inactivation gates: CLOSED
- Activation gates: OPEN
 Repolarization:
- Inactivation gates: OPEN
- Activation gates: CLOSED
All are university important MCQs.
Polarized membrane before action potential
Opening of Na-channels
DEPOLARIZATION: Sodium (Na) Influx
REPOLARIZATION: Potassium (K) Efflux
HYPERPOLARIZATION: Leakage of excess Potassium (K) ions
through the slow closing K channels.
HYPERPOLARIZATION: Sodium-Potassium Pump
Why does the depolarization not reach the
Nernst potential of +66mv for sodium?
There are 2 main reasons. At +35 mv:
 Sodium Influx stops because Inactivation gates of Sodium
channels close although the activation gates are open & thus
no sodium can enter
 Potassium Efflux starts because slow Potassium channel gates
open and potassium moves out.
Timing of opening and closing
of different gates
Can you differentiate ?
It is the time period between the application of a stimulus and the
start of the response (Action Potential)
When during the transit changes in the action potential, the Potential
difference between the inside of the membrane (-90mv) and outside
(0mv) decreases it is called depolarization. ( the tracing will move
upwards in the AP diagram)
A return to the resting membrane potential from either direction (i.e.
de- or hyper-polarization) is called repolarization.
HYPERPOLARIZATION: When during the transit changes in the action
potential, the Potential difference between the inside of the
membrane (-90mv) and the outside (0mv) increases it is called
 It is the basic structural and
functional unit of nervous system
 Axons vary in length from less than
a millimeter in neurons that
communicate only with
neighboring cells to longer than a
meter in neurons that
communicate with distant parts of
the nervous system or with
peripheral organs. For example,
the axon of the neuron innervating
your big toe must traverse the
distance from the origin of its cell
body within the spinal cord in the
lower region of your back all the
way down your leg to your toe.
 Why and how does the action potential spread in the forward
direction only?
 Why does NOT the action potential spread in the reverse
Propagation of action potential
Propagation of action potential
Propagation of action potential
Direction of propagation
Unmyelinated Nerve fiber
 Once an action potential is initiated at the axon hillock, no further
triggering event is necessary to activate the remainder of the nerve
fiber. The impulse is automatically conducted throughout the
 For the action potential to spread from the active to the inactive
areas, the inactive areas must somehow be depolarized to
threshold. This depolarization is accomplished by local current flow
between the area already undergoing an action potential and the
adjacent inactive area
 This depolarizing effect quickly brings the involved inactive area to
threshold, at which time the voltage-gated Na channels in this
region of the membrane are all thrown open, leading to an action
potential in this previously inactive area. Meanwhile, the original
active area returns to resting potential as a result of K efflux.
 Speed ranges between 0.25-100 m/sec in small to large nerev fiber
VIVA Question:
Does the action potential become weak (decremental) as it
travels down the nerve fiber?
 NO, the action potential does NOT become weak as it travels
down the nerve fiber. In fact, the AP does NOT travel down
the nerve fiber but triggers a new AP in every new part of the
membrane. It is like a “wave” at a stadium. Each section of
spectators stands up (the rising phase of an action potential),
then sits down (the falling phase) in sequence one after
another as the wave moves around the stadium. The wave,
not individual spectators, travels around the stadium.
 Thus, the last action potential at the end of the axon is
identical to the original one, no matter how long the axon is.
In this way, action potentials can serve as long-distance signals
without becoming weak or distorted or decremental.
VIVA Question:
Why does NOT the action potential spread in the reverse
 If AP were to spread in both directions, which is forward and
backward, it would be chaos, with the numerous AP’s
bouncing back & forth along the axon until the axon
eventually fatigued. This does not happen due to the
Refractory period. During and after the generation of an AP,
the changing status of the voltage-gated Na and K channels
prevents the AP from being generated in these areas again.