What is meant by a voltage-gated ion channel
- V = I*R, and in this case resistance is not constant (it is a function of membrane potential)
- The more positive the membrane potential, the more conductive the ion channel.
What structural features underlie the voltage-dependence of a “voltage-gated ion channel”?
The S4 sub-unit is:
- POSITIVELY charged and voltage sensitive
- full of argenine amino acids
- As membrane is hyperpolarised, argenine in the S4 rushes inward, gate closes, no longer conductive
Describe the kinetics of a typical axonal voltage-gated SODIUM channel opening in response to a voltage step from -80mV to 0mV
– +ve reversal potential –
at zero membrane potential, we have -ve current = INward
at -ve potential, we have no current (no conductivity)
at +ve potential, we have outflow trending linearly with potential
Looks like GELU function
When the membrane potential goes from -80 mV to 0 mV, Na+
channels rapidly open with a short delay of ~10 µs, but then, Na+ channels close again after ~200 µs and remain closed as long as the membrane potential is depolarized.
Describe the kinetics of a typical axonal voltage-gated POTASSIUM channel opening in response to a voltage step from -80mV to 0mV
– -ve reversal potential –
at zero membrane potential, we have +ve current = OUTward
at -ve potential, we have no current (no conductivity)
at +ve potential, we have outflow trending linearly with potential
Looks like a ReLU function (R in ReLU ~= the P in potassium)
When the membrane potential goes from -80 mV to 0 mV, K+ channels open, but with a longer delay of ~200 µs, and remain open as long as the membrane potential is depolarized.
Is Na or K flow explosive or stabilising? Why?
Think of the voltage-dependent current vs voltage plots of Na/K as we move up to -40mV - the activation point of these channels
Na+:
More voltage => INward current => more voltage [EXPLOSIVE]
K+:
More voltage => OUTward current => less voltage voltage [STABLE]
What are the reversal potentials of N+, K+, Cl-, Ca2+
Na+: +60mV
K+: -90mV
Cl-: -85mV
Ca: +123mV
What is the timescale of ion channels vs voltage-gated ion channels?
Ion channels is on microsecond timescale, voltage gated kinetics is hundreds of microseconds
Describe the recovery from inactivation of a typical axonal voltage-gated sodium channel.
It takes about 2-3ms to recover from inactivation
VG Na+ channels are activated by depolarization but
rapidly inactivate. To recover, the membrane potential
needs to return to hyperpolarized values. The
recovery time course can be measured by imposing 2
depolarizing voltage steps to the membrane and
varying the time interval between the two steps.
When the time interval is very short, VG Na+ channels
do not have time to fully recover from inactivation,
therefore the transient current evoked by the second
voltage step is reduced. As the time-interval increases,
VG Na+ channels recover more from inactivation and
the current evoked by the second step increases, until
it reaches the same amplitude as the for the first
voltage step.
Describe Na+ vs K+ ion channel diversity
Na+:
- encoded by one of 9 genes
- these genes will individually encode all 4 sub-units (and 6 transmembrane domains/proteins of each) starting with C terminal, ending with N
- beta subunit is small, bonds tightly with alphas
K+:
- one gene (of ~80 possible) encodes all 6 proteins for a given subunit, but different genes per subunit.
Describe the sequence of events underlying the action potential?
- Voltage goes up to above -40mV
- Inward current of Na+ leads to depolarisation, which becomes explosive
- ~200us later this slows
- When the current of Na+ slows, and 2us delay since voltage activation threshold is met, K+ is outflowed to restore the membrane potential.
- Repolarisation, refractory period (for some ms)
What determines the amplitude and time-course of the AP?
- The pace of the opening and closing of voltage-gated channels
- Conductances of the sodium and potassium ion channels
- density along axons of “”
- types of “”
Different classes of neurons can fire at different maximal frequencies. Why might that be?
Different refractory periods, as defined by pace of K+ channel kinetics
- GABAergic allows for rapid repolarisation, and so quicker refractory
- Glutamatergic is slower
Where does the action potential usually initiate? Why?
Initial segment. The protein Ankyrin G binds to both the neuron cytoskeleton (internals of an axon) and Na+ ion channels. This anchors the channels, and ensures their being clustered together in the initial segment so to LOWER the voltage activation threshold for APs.
What underlies action potential PROPOGATION?
a strong I_Na+ that will depolarize that part of the cell membrane
but also the nearby areas, where other VG Na+ channels will be activated, thus driving a new regenerative spike. Refractory period ensures unidirectionality
What are the key determinants of action potential propagation velocity?
- Membrane resistance must be high to ensure escape of current
- Axon resistance must be low
- Membrane capacitance must be low (charge isn’t lost to membrane)
these are ensured by MYELINATION: - Increases axonal membrane resistance by ~500x
- Increases AP speed from 1m/s to 100m/s
Myelin sheath is made from Glial cells / Schwann cells
Also high Na+ concentrations in Nodes of Ranvier
What are the time and space constants?
Space = sqrt(R_membrane / R_axial) [large = longer]
Time = R_m * C_m [small = quick]
Salut ambreee
