Define Action potential
A rapid change in the membrane potential depolarization followed by a return to the resting membrane potential.
Functions of Action Potentials (2)
Basis of signal transmission of excitable cells (nerve, muscle) and Initiation of muscle contraction
Action potentials are the same size and shape along the whole length of a nerve or muscle cell but
vary in size and shape between cells.
Microelectrode measurement of resting membrane potential (Em) about (voltage)
-90 mV at rest.
Subthreshold responses are
the local response.
Passing a small current into the cell causes
hyperpolarization (-90 to -100 mV).Drawing a small current out of the cell results: in depolarization (-90 to 70 mV).
Spread For hyperpolarization or depolarization is called
(local response)
For hyperpolarization or depolarization (local response) The size of the voltage response decreases
exponentially with distance from the point of current passage.
For hyperpolarization or depolarization (local response)The distance it takes for the voltage response to decay about 37% of its original size is called
the length constant of the cell.
For hyperpolarization or depolarization (local response)Typically length constants are on the order of
1 to 3 mm.
For hyperpolarization or depolarization (local response) A membrane with a long length constant will have _____ current decay than an (identical) membrane with a short length constant
less
If progressively larger depolarizing currents are passed, a point is reached at which
an action potential fires.
Action potentials differ from local responses because
they are larger and actively propagate along a cell membrane without decrement.
Are Action potential all or none?
Yes
Define Threshold
the membrane potential that is sufficient for the triggering of an action potential (-60 mV).
Define Overshoot
value of the membrane potential that is reached at the peak of the action potential (+50 mV).
Define Hyperpolarizing afterpotential
transient hyperpolarization after the repolarization phase of the action potential.
In giant squid The resting membrane potential is about
-70 mV
In giant squid
action potentials peak at Em =+50mV
It had been known for decades that the conductance increases during the action potential and that Na+ current was involved in depolarization. Hodgkin and Huxley in the early 1950's
unraveled the ionic currents involved in the action potential of squid giant axon. These conductance changes explain the shape of the action potential.
The basis for knowledge of the mechanism of the action potential is
The voltage clamp technique. Electronic feedback is used to set Em at whatever level the experimenter desires. The voltage clamp amplifier then keeps the Em at the level and measures the net ionic current that flows across the membrane.
Net transmembrane current flows when
squid giant axon is clamped to 0 mV.
How to Dissecting out the K+ current and Na+ current from net transmembrane current
Block K+ with TEA, Block Na+ with tetrodotoxin
gNa increases rapidly during ______, then
the early part of the action potential, then gNa decreases rather rapidly.
gK increases more _____ and reaches peak ________, and then
increase more slowly and reaches a peak at about the middle of the repolarization phase, and then returns more slowly to resting levels.
Increase gNa causes membrane potential to move towards ENa (+60mV) but
only reaches +50 mV because gK increase and because gNa decreases quickly.
Hyperpolarization afterpotential, gNa
is low and gK remains elevated thus pulling Em to EK (-100 mV) for a short time.
Mechanisms of action potential generation
Ionic channels in the membrane have gates. There are many more channels in the membrane than those which are "open" at rest.
At most only a _____ fraction of the Na+ channels are open at rest. A significantly ______ fraction of the K+ channels are open at rest.
At most only a small fraction of the Na+ channels are open at rest. A significantly larger fraction of the K+ channels are open at rest.
Ionic channels are sensitive to membrane potentials and undergo conformational changes with depolarization which alters the probability of the channel being open.
conformational changes with depolarization which alters the probability of the channel being open.
Critical requirement for initiating an action potential is that depolarization
increases, for a brief period of time, the probability of a Na channel being open. WTF?
Voltage-gated Na+ channels are Responsible for (2 things) the electrical excitability of both nerve and muscle membranes 2 things
the electrical excitability of both nerve and muscle membranes.
Two voltage dependent processes (gates) include
activation gate and inactivation gate
Activation gate controls
the rate and voltage dependence of permeability increase following depolarization. Charge within the membrane is rearranged when voltage-gated Na+ channels open (↑open channels = ↑permeability). Permeability is the "leakiness" of membrane to a particular ion.
Inactivation gate controls
the rate and voltage dependence of subsequent return of permeability to the resting level (blocks ion movement) during a maintained depolarization.
Ion selectivity
Na+ = Li+ > K+ > Rb+ > Cs+
Unit conductance
12-18 pS = 107 ions/sec/channel.
List Neurotoxins that act on Na channel
Tetrodotoxin, Saxitoxin (STX), Veratridine
In purified Na+ channel Integral membrane glycoprotein complex size
(- 316,000 Da)
In purified Na+ α subunit
270,000 Da
In purified Na+ β1 subunit
39,000 Da
In purified Na+ β2 subunit
37,000 Da
alpha subunit consists of
a single polypeptide with four repetitions of six membrane-spanning alpha-helical domains. Pore region believed to be formed from a stretch of amino acids between S5 and S6.
The S4 model of voltage sensor suggests
that the channel activation is caused by a conformational change within the conserved positively charged S4 region of each protein subdomain
The absolute refractory period is due to _______. No matter.....
voltage-dependent inactivation of many Na+ channels. An action potential cannot be generated no matter how strongly the cell is stimulated because the Na channels can't open.
Describe Relative Refractory Period
some Na+ channels are voltage inactivated and some of the K+ channels are open, both of which make it more difficult to depolarize the membrane to threshold.
The strength-duration curve
The strength of a stimulus and the length of time it must be applied to generate an action potential are inversely related.