What is the trend in peak Na and peak K conductances with voltage?
They both increase steadily from -50mV to 100mV, then plateaus.
gK has a lower conductance that gNa.
What does the graph of gNa and gK conductances against voltage look like?
See picture
S shaped curve - sigmoidal.
What is the Na and K channel current vs voltage plot?
See picture
What is the Na and K conductance vs voltage plot?
See picture
What is the relationship between membrane conductance and number of open channels?
Membrane conductance is proportional to the number of open channels.
At 0 conductance, there is no Na+ channels open.
At the plateau of the conductance curve, there are 100% of Na+ channels open.
See picture of a conductance vs voltage plot.
What is the relative difference in Na+ and K+ conductance?
Na+ has higher conductance than K+.
This is because the density (number) of Na+ channels is greater than that of K+ channels.
Using the data (see picture), what is the percentage of the total population of Na+ channels open at -20mV?
35%
Conductance is proportional to the number of open ion channels, so all channels are open when the conductance reaches its peak (110mV).
So the percentage of open channels at -20mV = conductance at -20mV / conductance at 110mV x by 100.
What percentage of the total population of K+ channels is open at -20mV?
49%
Conductance is proportional to the number of open ion channels, so all channels are open when the conductance reaches its peak (110mV).
So the percentage of open channels at -20mV = conductance at -20mV / conductance at 110mV x by 100.
What percentage of the total population of K+ channels is open at +20mV?
83%
What is V1/2?
The voltage at which half of the maximal number of channels is open.
What is the V1/2 value for VGNaC?
-10mV
Take the maximum conductance value for Na+, divide by 2, and find the value on the graph to correlate to the voltage.
What is the V1/2 value for VGKC?
-20mV
Take the maximum conductance value for Na+, divide by 2, and find the value on the graph to correlate to the voltage.
Why are the maximum conductance values different for the VGNaC vs the VGKC?
There are more Na+ channels than K+ channels.
It is not related to the driving forces of the ions because conductance is dependent only on the activity of the channels, (current depends on driving force).
How do you calculate membrane current from conductance measurements?
Conductance = current / driving force.
Driving force = test voltage - equilibrium potential.
So gNa = INa / (Vm-55mV)
So INa = gNa x (Vm-55mV)
What is Na current for each of these values?
Test voltage -20mV, peak Na conductance 0.02.
Test voltage +20mV, peak Na conductance 0.04
Test voltage +60mv, peak Na conductance 0.05.
Test voltage -20mV, peak Na conductance 0.02, Na current = -1.5.
Test voltage +20mV, peak Na conductance 0.04, Na current = -1.4
Test voltage +60mv, peak Na conductance 0.05, Na current = 0.25
What does a negative calculated Na peak current value mean?
The voltage-clamp amplifier is passing negative current to counterbalance the effect of Na+ ions entering the cell via voltage-gated channels.
What does the negative calculated Na peak current value not mean?
It is not negative because of outward movement, it is inward movement because the test voltages are more negative than equilibrium potential for Na+.
Even if it was outward movement, this would hyperpolarise the membrane, and the voltage clamp amplifier would inject positive current to counterbalance the negative charge.
What is the graph with Na+ and K+ conductances activated from -65mV and -20mV?
see picture
What happens when the starting voltage is set to -20mV instead of -65mV?
The maximal Na+ conductance is very small but maximal K+ conductance is unaffected.
Na+ channels inactivate due to the inactivation segment between the 3rd and 4th domains in the alpha subunit, which is added by depolarisation. K+ channels do not inactivate, so the current is still present, and reaches maximum. The current starts higher because some of the VGKC are activated already at the holding membrane -20mV.
In simulations only delayed rectigier VGKC are present.
How can the Na+ and K+ currents activated from -65mV and -20mV be described?
Persistent current for K+.
Inactivating current for Na+ at -20mV.
There is a current before it is activated at -20mV because some of the channels open before this voltage.
change this
see picture.
How many times is the Na+ and K+ channels densities reduced by half to block the action potential (simulating lidocaine)?
The densities are halved 4 times
For the lidocaine experiment, what is the percentage reduction in Na+ conductance needed to prevent an action potential for local anaesthetics?
Assume Na+ conductance is directly equivalent to channel density.
97%.
The action potential is blocked when depolarisation fails to increase above the level provided by the stimulation.
The percentage reduction in density is the remaining Na+ channel density divide by the starting density (0.12).
Then subtract this from 100.
What is tetrodotoxin?
TTX is a highly specific blocker of Na channels.
It does not affect K channels.
The effects can be mimiced on a simulation by selectively reducing the value of Na channel density but not K channel density.
How many times must we reduce the Na channel densities by half to block the action potential for tetrodotoxin?
Three times.
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