ACTION POTENTIAL:

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ACTION POTENTIAL

• Dr. Ayisha Qureshi
• Assistant Professor
• MBBS, MPhil

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DEFINITIONS

• Stimulus
• 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.

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REMEMBER

• IMPORTANT
• Sodium voltage-gated channels are fast channels
  have 2 gates
• - An outer Activation gate(closed in resting
  state)
• - An Inner 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 separately.

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Sodium Potassium voltage-gated channels
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Action potential
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Action Potential

• Definition
• An Action Potential is a self-propagating wave of
  electro-negativity that passes along the surface
  of the axolemma of the nerve fibers.

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• We know that the inside of the nerve membrane is
  negative with respect to the outside
  (RMP90 mv)
• When an effective stimulus(threshold or
  suprathreshold) is applied, the electrical charge
  on the membrane is reversed at the active part
  of the nerve fibre the outside becomes negative
  as compared to the corresponding region in the
  interior. This is called DEPOLARIZATION and forms
  the Action Potential.

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PHASES OF AN ACTION POTENTIAL

• Phase 1 Depolarization
• Phase 2 Repolarization
• Phase 3 Hyperpolarization

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IONIC BASIS OF AN ACTION POTENTIAL

1. DEPOLARIZATION Sodium (Na) Influx
2. REPOLARIZATION Potassium (K) Efflux
3. HYPERPOLARIZATION Leakage of excess Potassium
   (K) ions through the slow closing K channels.
4. RETURN OF THE AP TO THE RMP FROM
   HYPERPOLARIZATION Sodium-Potassium Pump

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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.

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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

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VIVA QUESTIONS

• AFTER-DEPOLARIZATION
• The descending limb of the action potential does
  not reach the baseline abruptly, but it shows a
  delay of several milliseconds. This is due to
  decreased rate of K efflux at this time. The
  excitability conductivity of the fibre are
  increased during this phase.
• AFTER-HYPERPOLARIZATION
• Same as Hyperpolarization....

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DEFINITIONS

• LATENT PERIOD
• It is the time period between the application of
  a stimulus and the start of the response (Action
  Potential)
• DEPOLARIZATION
• 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)
• REPOLARIZATION
• 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 Hyperpolarization.

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PROPAGATION OF AN ACTION POTENTIAL

• Conduction of an Action Potential in an
  Unmyelinated nerve fibre

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Question

• Why and how does the action potential spread in
  the forward direction only?
• Why does NOT the action potential spread in the
  reverse direction?

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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
  neuron.
• 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.

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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.

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• 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.

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VIVA Question

• Why does NOT the action potential spread in the
  reverse direction?
• If AP were to spread in both directions, which is
  forward and backward, it would be chaos, with the
  numerous APs 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.

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Conduction of ap in a Myelinated nerve fiber
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Continuous Conduction

• Occurs in unmyelinated axons.
• In this situation, the wave of de- and
  repolarization simply travels from one patch of
  membrane to the next adjacent
  
  patch.
• APs moved
  in this fashion
  
  along the
  sarcolemma
  
  of a muscle
  fiber
  as well.
• Analogous to
  dominoes
  
  falling.

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• In a Myelinated Nerve Fibre an Action Potential
  travels by SALTATORY Conduction, which is in a
  jumping manner from one Node of Ranvier to the
  next Node of Ranvier, While in an Unmyelinated
  Nerve Fibre an Action Potential travels from
  POINT TO POINT.
• At the nodes of ranvier, there are an increased
  number of Sodium channels present.

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• Which do you think has a faster rate of AP
  conduction myelinated or unmyelinated axons?

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• The answer is a myelinated axon.
• If you cant see why, then answer this question
  
• Could you move 100ft faster if you walked
  heel to toe or if you bounded in a way that there
  were 3ft in between your feet with each step?

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• Which do you think would conduct an AP faster
  an axon with a large diameter or an axon with a
  small diameter?

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• The answer is an axon with a large diameter.
• If you cant see why, then answer this question
  
• Could you move faster if you walked through a
  hallway that was 6ft wide or if you walked
  through a hallway that was 1ft wide?

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Name the events ions responsible for

• Depolarization
• Repolarization
• Hyperpolarization OR Undershoot
• Return of the AP from the Overshoot to the RMP

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Properties of A nerve fibre
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1. ALL OR NONE LAW

• (also called the All or Nothing Law)
• On application of a stimulus, an excitable
  membrane either responds with a maximal or
  full-fledged action potential that spreads along
  the nerve fiber, or it does not respond with an
  action potential at all. This property is called
  the all-or-none law.
• (This is in direction proportion to the strength
  of the stimulus applied.)
• e.g This is similar to firing a gun. Either the
  trigger is NOT pulled sufficiently to fire the
  gun (subthreshold stimulus) OR it is pulled hard
  enough to fire the gun (threshold is reached).
  Squeezing the trigger harder does not produce a
  greater explosion, just as pulling the trigger
  halfway does not cause the gun to fire halfway.

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Some Action Potential Questions

• What does it mean when we say an AP is all or
  none?
• Can you ever have ½ an AP?
• How does the concept of threshold relate to the
  all or none notion?
• Will one AP ever be bigger than another?
• Why or why not?

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- Absolute refractory period- relative
Refractory period

• 2. Refractory period

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2a ABSOLUTE REFRACTORY PERIOD

• Definition
• Once an action potential has been generated , the
  time period during which even a suprathreshold
  stimulus will fail to produce a new action
  potential is called the Absolute Refractory
  period.
• During this time the membrane becomes completely
  refractory (stubborn or unresponsive) to any
  further stimulation.
• It corresponds to the entire Depolarization phase
  most of the Repolarization phase.
• Due to Absolute refractory period, one AP must be
  over before another can be initiated at the same
  site. APs cannot be overlapped or added one on
  top of another.

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• BASIS OF AN ABSOLUTE REFRACTORY PERIOD
• During the depolarization phase of AP, the
  voltage-gated Sodium channels have still NOT
  reset to their original position. For the Sodium
  channels to respond to a stimulus, 2 events are
  important
• Sodium channels be reset to their closed but
  capable of opening position. i.e inactivation
  gates open and activation gates closed.
• The Resting membrane potential must be
  re-established.

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2b Relative Refractory Period

• Definition
• Following the absolute refractory period is seen
  a period of short duration during which a second
  action potential can be produced, only if the
  triggering event is a suprathreshold stimulus.
  This period is called the Relative Refractory
  Period.
• It corresponds to the last half of the
  Repolarization phase.

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• Basis of a Relative Refractory Period
• An action potential can be produced by a
  suprathreshold stimulus because of the following
  reasons
• By the end of the repolarization phase, some Na
  channels have reset while some K channels are
  also still open.
• Thus, a greater than normal triggering event
  (suprathreshold stimulus) is required to produce
  an AP.

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Absolute VS Relative Refractory Period

• Imagine, if you will, a toilet.
• When you pull the handle, water floods the bowl.
  This event takes a couple of seconds and you
  cannot stop it in the middle. Once the bowl
  empties, the flush is complete. Now the upper
  tank is empty. If you try pulling the handle at
  this point, nothing happens (absolute
  refractory). Wait for the upper tank to begin
  refilling. You can now flush again, but the
  intensity of the flushes increases as the upper
  tank refills (relative refractory)

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In this figure, what do the red and blue box
represent?
VM
TIME
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What is the significance of the REFRACTORY PERIOD
(both absolute relative)

1. There is no fusion or summation of the action
   potentials. This intermittent, ie. Not continuous
   conduction of nerve impulses is one of the
   reasons why a nerve fibre can respond to
   continuous stimulation for hours without getting
   tired. Thus, it decreases fatigue in a nerve
   fibre.
2. The Action Potentials are produced separate from
   each other. So, a new AP is produced in each part
   of the nerve fibre. This ensures that the AP does
   not die out as it is conducted along the
   membrane.
3. Only a certain number of Action Potentials can be
   produced in a nerve fibre because the interval
   between any 2 action potentials cannot be shorter
   than the Absolute Refractory Period. This
   prevents fatigue of the nerve fibers and sets an
   upper limit on the maximum numbers of AP that can
   be produced in a nerve fibre in a given period of
   time.
4. By the time the original site has recovered from
   its refractory period and is capable of being
   restimulated by normal current flow, the action
   potential has been propagated in the forward
   direction only and is so far away that it can no
   longer influence the original site. Thus, the
   refractory period ensures the one-way propagation
   of the action potential down the axon away from
   the initial site of activation.

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3. Compound action potential
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3. Compound Action Potential is seen in a nerve
trunk NOT a nerve fibre

• An action potential having more than one
  peak/spike is called a Compound action potential.
• CAUSE A nerve trunk contains many nerve fibres
  differing widely in their excitability
  different speeds of conduction of AP. Multiple
  peaks are recorded with the AP from fastest
  conducting nerve fibre first to be recorded
  followed by the slower ones....

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4. Strength-duration curve
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4. Strength Duration Curve

• Strength duration curve represents 2 (two)
  factors which control the final strength of the
  stimulus. These are
• Voltage or current strength of the stimulus
  applied
• Duration of the stimulus
• By varying the above 2 factors and plotting the
  results, a curve is obtained which is called the
  STRENGTH-DURATION CURVE. (See Mushtaq, vol. 1,
  ed. 5th , page 118-119)
• It is obvious that a stimulus with a low voltage
  will have to be applied for a long period of time
  to reach the threshold level, while high voltage
  stimulus will need a much shorter duration....

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4. Strength Duration Curve

• RHEOBASE
• It is the minimum voltage stimulus which when
  applied for an adequately prolonged time will
  produce an AP.
• UTILIZATION TIME
• The minimum time that a current equal to rheobase
  must act to induce an AP is called the
  Utilization Time.
• CHRONAXIE
• It is the minimum duration for which a stimulus
  equal to twice the rheobase value has to be
  applied in order to start an AP.
• Tissues which are more excitable will have a
  shorter chronaxie and vice versa...

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PROPERTIES OF AN ACTION POTENTIAL

• All or none Law
• Absolute Relative Refractory period
• Compound Action Potential
• Strength-Duration Curve
• Conduction through
• - A myelinated nerve fiber (Saltatory
  conduction)
• - An unmyelinated nerve fiber (Point to Point
  Conduction)