the action potential

THE ACTION POTENTIALTHE ACTION POTENTIAL

Properties of the Action PotentialProperties of the Action Potential

• The Ups and Downs of an Action Potential• Oscilloscope to visualize an AP

- Rising phase : rapid depolarization to reach the peak of 40mV

- Overshoot : part where inside neurons are more positive than outside (> 0mV)

- Falling phase : rapid repolarization

- Undershoot : after-hyperpolarization


• The Generation of an Action Potential

• Caused by depolarization of membrane beyond threshold - generator potential

• “All-or-none” - conversion of analog into digital

• Chain of events that lead to the generation of action potential in the thumbtack response

- The thumbtack press the skin

- The membrane of nerve fibers is stretched

- Na+ -permeable channels that are gated by mechanical stimulation open

- Na+ influx depolarizes the membrane

- The depolarization reaches the threshold

- Action potential


• The Generation of Multiple Action Potentials

• Continuous depolarizing current injection can cause multiple action potential generation


• The Generation of Multiple Action Potentials

• Firing frequency reflects the magnitude of the depolarizing current

- One way that stimulation intensity is encoded• There is a limit!

- Maximum firing frequency ~ 1000 Hz

- Absolute refractory period : time required to initiate the next AP once an AP is initiated ~ 1 msec

- Relative refractory period : for a few miliseconds after the end of absolute refractory period, current needed to reach threshold is above normal

The Action Potential, In TheoryThe Action Potential, In Theory

• Ideal cell has Na+-K+ pumps, K+-channels, and Na+-channels.

• Channels are closed (gK=0) and Vm=0 mV

• Potassium channels are open (gK>0)

• Outward current of K+

• IK (net movement of K+) >0 until Vm reaches EK

• Eventually Vm reaches EK, making driving force (Vm - E) equals zero

The Action Potential, In TheoryThe Action Potential, In Theory

• Rising phase

• At -80 mV, driving force for Na+ is (Vm-ENa = -80 mV - 62 mV = - 142 mV)

• When many Na+ channels open (gNa >> 0) at once because membrane is depolarized to threshold, the inward sodium current (INa)) is large - quickly brings Vm toward Ena (62 mV) assuming Na+ permeability is now far greater than K+ permeability

• Falling phase

• Sodium channels quickly close and potassium channels remains open

• Dominant membrane permeability switches back to potassium

• K+ flows out to bring Vm back to EK

• The speed of falling phase depends on the size of gK

The Action Potential, In RealityThe Action Potential, In Reality

• The Generation of an Action Potential

• gNa increases at the threshold and gK transiently increases during falling phase in reality?

• Hodgkin and Huxley proved it experimentally (1950) using

- Voltage Clamp method “Clamp” membrane potential at any chosen value then deduce

the changes in membrane conductance by measuring currents

- They proposed that the transient increase in gNa is possible due to

Existence of sodium “gates” in the axonal membrane

Gates are activated by depol. Over threshold

Gates are inactivated by a positive membrane potential

Gates are deinactivated only after membrane potential returns to a negative value


• The Voltage-Gated Sodium Channel

• A single polypeptide

• Four distinct domains

- Each domain contains 6 transmembrane alpha helices (S1-S6) and ion-selective pore loop

- They clump together to form a pore

- Selectivity filter deals with hydrated ions



• S4 has the voltage sensor in which positively charged amino acids are regularly spaced along the coils of helix

• Depolarization can twists S4 by electric repulsion

• Conformational change causes the gate to open


• The Voltage-Gated Sodium Channel : Functional Properties

• Patch-clamp method (Erwin Neher and Bert Sakmann) was developed in the mid-1970s

- Small patch of membrane seals the tip of an electrode

- The membrane is torn apart from the neuron

- Ion current can be measured at any clamped membrane potential


• Functional Properties of the Sodium Channel

• Open with little delay

• Stay open for about 1 msec

• Cannot be opened again by depolarization until the membrane potential returns to a negative value near thresholod

• Absolute refractory period

- Channels are inactivated by the second gate

- It is a slow one to act and needs to be replaced by the fast gate (deinactivation)

• Explains many properties of AP



• Generalized epilepsy with febrile seizures (channelopathy)

- Caused by a single amino acid change in the extracellular region of one sodium channel (out of many)

- Slowed inactivation prolongs action potential

• Toxins as experimental tools

- Puffer fish toxin: Tetrodotoxin (TTX)

Toshio Narahashi

Clogs Na+ permeable pore by binding tightly

Blocks all sodium-dependent action potentials

- Red Tide toxin: Saxitoxin

Na+ Channel-blocking toxin

Produced by marine protozoa, Gonyaulax dinoflagellate, typical shellfish prey

Occasional blooming of the dinoflagellates cause red tide

• Structural studies and physiological studies


• Voltage-Gated Potassium Channels

• According to Hodgkin and Huxley’s experiments, falling phase cannot be explained solely by the inactivation of gNa

• Existence of potassium gate was also proposed

- open in response to depolarization

- Potassium gates open slowly (need about 1msec after depol.)

• Delayed rectifier

- Potassium conductance serves to rectify or reset membrane potential

• Function to diminish any further depolarization

• Four separate polypeptide subunits join to form a pore


• Key Properties of the Action Potential

• Threshold

• Rising phase

• Overshoot

• Falling phase

• Undershoot

• Absolute refractory period

- sodium channel deinactivation

• Relative refractory period

- potassium channel closure (hyperpolarization)

Action Potential ConductionAction Potential Conduction

• Propagation

• Depolarized to threshold

• Sodium channels open

• Influx of Na+

• Positive charges coming in depolarize the membrane just ahead to threshold

• Next population of sodium channels open


• Propagation of the action potential

• Orthodromic

- Action potential travels in one direction - down axon to the axon terminal

• Antidromic (experimental)

- Backward propagation is possible if the initiation of AP occurs in the middle of axon

• Cannot turn back on itself

- Refractory (inactivated sodium channels)

• Typical conduction velocity: 10 m/sec


• Factors Influencing Conduction Velocity

• Depends on how far the depolarization ahead of the action potential spreads

• The spread depends on resistance of space

• Path of the positive charge

- Down the inside of the axon

- Across the axonal membrane - leakage

• Axonal excitability

- Axonal diameter (bigger = faster)

- Number of voltage-gated channels

• Neural pathway that are specially important for survival have evolved unusually large axons - squid giant axon


• Factors Influencing Conduction Velocity

• Layers of myelin sheath insulate the leakage of charges and facilitate current flow down the inside of axon

• Nodes of Ranvier

- Every 0.2-2.0 mm

- Place of AP generation

- Place of voltage-gated sodium channels

• Saltatory conduction

- AP travels by leaping


• Multiple sclerosis

• Demyelinating disease

• Marked slowing of conduction

• CNS version of Guillian-

Barre syndrome

Action Potentials, Axons, and DendritesAction Potentials, Axons, and Dendrites

• Spike-initiation zone

• Only membrane that contains voltage-gated sodium channels are capable of generating AP

• Axon hillock

• Sensory nerve endings

• Differences in the type and density of membrane ion channels can account for the characteristic electrical properties of different types of neuron

Bursting Tonic Adaptation

the action potential

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