Transcript Chapter 04: The Action Potential

THE ACTION POTENTIAL
Properties 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
Properties of the Action Potential
• 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
Properties of the Action Potential
• The Generation of Multiple Action Potentials
•
Continuous depolarizing current injection can cause
multiple action potential generation
Properties of the Action Potential
• 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 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 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 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 Action Potential, In Reality
• The Voltage-Gated Sodium Channel
•
A single polypeptide
•
Four distinct domains
- Each domain contains 6
transmembrane alpha helices (S1S6) and ion-selective pore loop
- They clump together to form a pore
- Selectivity filter deals with hydrated
ions
The Action Potential, In Reality
• The Voltage-Gated Sodium Channel
•
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 Action Potential, In Reality
• 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
The Action Potential, In Reality
• 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
The Action Potential, In Reality
• The Voltage-Gated Sodium Channel
•
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
The Action Potential, In Reality
• 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
The Action Potential, In Reality
• 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 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
Action Potential Conduction
• 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
Action Potential Conduction
• 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
Action Potential Conduction
• 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
Action Potential Conduction
• Multiple sclerosis
•
Demyelinating disease
•
Marked slowing of conduction
•
CNS version of GuillianBarre syndrome
Action 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