Transcript of the moving action potential.

Membrane potentials
膜电位
Xia Qiang, MD & PhD
Department of Physiology
Room C518, Block C, Research Building, ZJU School of Medicine
Tel: 88208252
Email: [email protected]
Electrocardiogram
ECG（心电图）
Electroencephalogram
EEG（脑电图）
Electromyogram
EMG（肌电图）
Extracellular Recording（细胞外记录）
Intracellular Recording
（细胞内记录）
Recording of membrane potentials
Video
Extracellular and Intracellular Recording
1. Extracellular recording in earthworm giant axons
2. Intracellular recording in crayfish muscle cells
Opposite charges attract each other and
will move toward each other if not separated
by some barrier.
Only a very thin shell of charge difference
is needed to establish a membrane potential.
Resting membrane potential
（静息电位）
A potential difference across
the membranes of inactive
cells, with the inside of the cell
negative relative to the outside
of the cell
Ranging from –10 to –100 mV
Overshoot refers to
the development of
a charge reversal.
A cell is
“polarized”
because
its interior
is more
negative
than its
exterior.
（超射）
Repolarization is
movement back
toward the
resting potential.
（复极化）
（极化）
Depolarization
occurs
when ion
movement
reduces the
charge
imbalance.
Hyperpolarization is
the development of
even more negative
charge inside the cell.
（去极化）
（超极化）
chemical
driving force
----------------++++++++++++++++
electrochemical
balance
electrical
driving force
The Nernst Equation:
German physical chemist and physicist
RT
[ Ion]o
E
log
ZF
[ Ion]i
K+ equilibrium potential (EK)

R=Gas constant
T=Temperature
Z=Valence
F=Faraday’s constant
(37oC) （钾离子平衡电位）
[ K ]o
Ek  60 log  (mV )
[ K ]i
Begin:
K+ in Compartment 2,
Na+ in Compartment 1;
BUT only K+ can move.
Ion movement:
K+ crosses into
Compartment 1;
Na+ stays in
Compartment 1.
At the potassium
equilibrium potential:
buildup of positive charge
in Compartment 1 produces an electrical potential that
exactly offsets the K+ chemical concentration gradient.
Begin:
K+ in Compartment 2,
Na+ in Compartment 1;
BUT only Na+ can move.
Ion movement:
Na+ crosses into
Compartment 2;
but K+ stays in
Compartment 2.
At the sodium
equilibrium potential:
buildup of positive charge in Compartment 2
produces an electrical potential that exactly
offsets the Na+ chemical concentration gradient.
Difference between EK and directly measured
resting potential
Ek
Observed RP
Mammalian skeletal muscle cell
-95 mV
-90 mV
Frog skeletal muscle cell
-105 mV
-90 mV
Squid giant axon
-96 mV
-70 mV
Goldman-Hodgkin-Katz equation
Role of Na+-K+ pump:
•Electrogenic
•Hyperpolarizing
Establishment of resting
membrane potential:
Na+/K+ pump establishes
concentration gradient
generating a small
negative potential; pump
uses up to 40% of the
ATP produced by that
cell!
Click here to play the
Sodium-potassium Pump
Flash Animation
Origin of the normal resting membrane
potential
K+ diffusion potential
Na+ diffusion
Na+-K+ pump
Action potential（动作电位）
Some of the cells (excitable cells) are capable to rapidly reverse their
resting membrane potential from negative resting values to slightly
positive values. This transient and rapid change in membrane potential
is called an action potential
A typical neuron action potential
Negative afterpotential
Spike potential
After-potential
Positive
after-potential
Electrotonic Potential（电紧张电位）
The size of a
graded potential
(here, graded
depolarizations)
is proportionate
to the intensity
of the stimulus.
Graded potentials can be:
EXCITATORY
or
INHIBITORY
(action potential (action potential
is more likely)
is less likely)
The size of a graded potential is proportional to the size of the stimulus.
Graded potentials decay as they move over distance.
Graded potentials decay as they move over distance.
Local response
（局部反应）
• Not “all-or-none” （全或无）
• Electrotonic propagation:
spreading with decrement
（电紧张性扩布）
• Summation: spatial &
temporal（时间与空间总和）
Threshold Potential（阈电位）: level of depolarization needed
to trigger an action potential (most neurons have a threshold
at -50 mV)
Ionic basis of action potential
(1) Depolarization（去极化）:
Activation of Na+ channel
Blocker:
Tetrodotoxin (TTX)
（河豚毒素）
(2) Repolarization（复极化）:
Inactivation of Na+ channel
Activation of K+ channel
Blocker:
Tetraethylammonium
(TEA)（四乙胺）
The rapid opening of voltage-gated Na+ channels
explains the rapid-depolarization phase at the
beginning of the action potential.
The slower opening of voltage-gated K+ channels
explains the repolarization and after hyperpolarization
phases that complete the action potential.
An action potential
is an “all-or-none”
sequence of changes
in membrane potential.
Action potentials result
from an all-or-none
sequence of changes
in ion permeability
due to the operation
of voltage-gated
Na+ and K + channels.
The rapid opening of
voltage-gated Na+ channels
allows rapid entry of Na+,
moving membrane potential
closer to the sodium
equilibrium potential (+60 mv)
The slower opening of
voltage-gated K+ channels
allows K+ exit,
moving membrane potential
closer to the potassium
equilibrium potential (-90 mv)
Click here to play the
Voltage Gated Channels
and Action Potential
Flash Animation
Mechanism of the
initiation and
termination of AP
Re-establishing Na+ and K+
gradients after AP
Na+-K+ pump
“Recharging” process
Properties of action potential (AP)
•Depolarization must exceed threshold
value to trigger AP
•AP is all-or-none
•AP propagates without decrement
How to study ?
Voltage Clamp
Nobel Prize in Physiology or
Medicine 1963
"for their discoveries concerning the ionic
mechanisms involved in excitation and
inhibition in the peripheral and central
portions of the nerve cell membrane"
Eccles
Hodgkin
Huxley
Currents recorded under voltage
clamp condition
Patch Clamp
Nobel Prize in Physiology or
Medicine 1991
"for their discoveries concerning the
function of single ion channels in cells"
Erwin Neher
Bert Sakmann
Video
The Squid and its Giant Nerve Fiber
"The Squid and its Giant Nerve Fiber" was filmed
in the 1970s at Plymouth Marine Laboratory in England.
This is the laboratory where Hodgkin and Huxley
conducted experiments on the squid giant axon in the
1940s. Their experiments unraveled the mechanism of
the action potential, and led to a Nobel Prize. Long out
of print, the film is an historically important record of
the voltage-clamp technique as developed by Hodgkin
and Huxley, as well as an interesting glimpse at how the
experiments were done.
Video
Patch Clamp
Conduction of action potential（动作电位的传导）
Continuous propagation
in the unmyelinated axon
Click here to play the
Action Potential Propagation
in an Unmyelinated Neuron
Flash Animation
Saltatory propagation in
the myelinated axon
http://www.brainviews.com/abFiles/AniSalt.htm
Saltatorial Conduction: Action potentials jump from one node to the
next as they propagate along a myelinated axon.
（跳跃性传导）
Click here to play the
Action Potential Propagation
in Myelinated Neurons
Flash Animation
Excitation and Excitability
（兴奋与兴奋性）
To initiate excitation (AP)

Excitable cells

Stimulation
 Intensity
 Duration
 dV/dt
Strength-duration Curve（强度-时间曲线）
Threshold intensity
（阈强度） &
Threshold stimulus
（阈刺激）
Four action potentials,
each the result of a
stimulus strong enough to
cause depolarization, are
shown in the right half of
the figure.
Refractory period following an AP:
1. Absolute Refractory Period: inactivation of Na+ channel
（绝对不应期）
2. Relative Refractory Period: some Na+ channels open（相
对不应期）
Factors affecting excitability
Resting potential
Threshold
Channel state
The propagation of the action potential from the dendritic
to the axon-terminal end is typically one-way because the
absolute refractory period follows along in the “wake”
of the moving action potential.
SUMMARY
Resting potential:



K+ diffusion potential
Na+ diffusion
Na+ -K+ pump
Graded potential



Not “all-or-none”
Electrotonic propagation
Spatial and temporal summation
Action potential


Depolarization: Activation of voltage-gated
Na+ channel
Repolarization: Inactivation of Na+ channel,
and activation of K+ channel
Refractory period


Absolute refractory period
Relative refractory period
Case
Primary Hyperkalemic Periodic Paralysis (原发性高血钾性周期性麻痹)
A l0-year-old boy has sporadic attacks of muscle paralysis. The patient has four brothers, all of whom
have suffered similar symptoms. The onset of these attacks is characterized by pain associated with
contractures of the affected muscles. Later in the attack those muscles may become paralyzed and
more flaccid. Episodes of pain and contracture frequently occur without subsequent paralysis. Analysis
of blood samples taken during an attack indicates that the patient is hyperkalemic. Plasma K+ levels
are normal when the patient is not having an attack. Biopsies of the patient's muscle show a
significantly diminished level of intracellular K+ (83 mmol/kg wet tissue) compared with control
muscle (95 mmol/kg wet tissue). Basal tissue activity of Na+, K+-ATPase is normal. Paralytic attacks
are accompanied by diuresis with increased K+ excretion. Electrophysiologic studies of the patient
show that during an attack the excitability and conduction times of motor neurons are normal, as is
the function of the neuromuscular junction. Microelectrode studies show that during an attack the
magnitude of the resting membrane potential of skeletal muscle cells is diminished compared with
control muscle fibers. Electromyography shows that early pared with control muscle fibers.
Electromyography shows that early in an attack the muscle contractures are associated with
spontaneous action potentials in the affected muscle fibers. Later, during the paralytic phase of an
attack, muscle cells become electrically inexcitable - the muscle cells do not respond electrically to
stimulation of the motor axons that innervate them. A paralytic attack can be relieved by treating the
patient with an insulin injection. Long-term administration of the 2-agonist salbutamol dramatically
diminishes the occurrence of episodes of both contractures and subsequent paralytic attacks.
Questions
l. What might account for the patient being hyperkalemic during an attack,
while the potassium concentration in his skeletal muscle cells is diminished?
What types of alterations of basic cellular processes might underlie this
situation?
2. What explains the observation that the magnitude of the resting membrane
potentials of the patient's skeletal muscle fibers is diminished during an
attack?
3. Does the diminished resting membrane potential have anything to do with
the spontaneous action potentials and contractures that occur early in an
attack, before paralysis sets in?
4. How might the diminished resting membrane potential contribute to the
paralytic phase of an attack, in which muscle cells are electrically
inexcitable?
5. How might insulin terminate a paralytic attack?
6. How might long-term administration of salbotamol diminish the occurrence
of attacks of contractures and paralysis?
Answers
l. The hyperkalemia with a concomitant decrease in the amount of K+ in muscle cells suggests that the hrperkalemia is
caused bf K+ efflux from the cells, but the cause of K+ efflux is not known. Net K+ efflux from muscle cells might
occur because of diminished fate of K+ accumulation by the Na+, K+-ATPase, or an increased rate of K+ efflux
from the cell, or a combination of both factors. The observation that Na+, K+-ATPase is normal does not
completely rule out a malfunction of this protein during an attack.
2. Elevating extracellular K+ and decreasing the intracellular level of K+ would decrease the potassium equilibrium
potential and thus decrease the magnitude of the resting membrane potential.
3. The decreased magnitude of the resting membrane potential initially brings the muscle cells closer to threshold for
firing an action potential. For this reason, spontaneous, small fluctuations in the resting membrane potential may
reach threshold. This results in spontaneous action potentials and contractions of skeletal muscle cells and leads
to the contractures experienced by the patient early in an attack.
4. Prolonged depolarization of the muscle cell plasma membrane will lead to voltage inactivation of Na+ channels in
the membrane, which will result in the muscle cell's being unable to fire an action potential. This is believed to be
the cause of the paralytic phase of an attack and is supported by the observation that during the paralytic phase,
the patient's skeletal muscle cells may be electrically inexcitable.
5. Insulin immediately and powerfully promotes the uptake of K+ by cells and the extrusion of Na+ from cells.
Administration of insulin thus corrects the hyperkalemia restores cellular K+ levels toward normal, and causes the
resting membrane potential for the affected skeletal muscle cells to become closer to the normal resting value. In
this way insulin is believed to terminate an attack of contractures or paralysis in these patients.
6. Long-term administration of salbutamol, a β2-agonist, increases the activity of the Na+, K+-ATPase in skeletal
muscle cells. In this way, salbutamol administraion leads to increased sequestration of K+ in muscle cells.
Apparently this helps to prevent the K+ efflux that underlies episodes of hyperkalemia with resultant contractures
that may be followed by periods of paralysis.
THANK YOU FOR YOUR
ATTENTION!