Is there any case in which excitability increases with lowering the RMP?

Question

My professor says , at a more negative RMP, less sodium ion channels are inactivated, so if you take 2 of the exact same neuron with the same threshold potentials, and try to excite them starting from different membrane potentials, the one you try to excite from a more negative membrane potential excites faster and fires an action potential faster because more sodium ion channels are activated .

I might have missed something from what he said, and I hope I did because this makes no sense to me. Shouldn't excitability increase with an increasing positive resting membrane potential ? The closer I am to the threshold potential the weaker the stimulus that I need to fire an action potential, isn't that right ?

The only article I found on this is https://www.sciencedirect.com/topics/neuroscience/excitability and its specific to cardiac muscle so perhaps the excitability in cardiac muscle is an exception ?

Answer 1

A typical voltage-gated sodium channel has 3 gating states: open, closed, and inactivated. The third category is the important one here.

Open channels are open: they let ions through.

Closed channels are closed: they don't let ions through, however, they are available to open and their probability of opening increases as the membrane voltage rises from negative towards positive.

Inactivated channels don't pass ions, but it also cannot be opened by depolarized voltage. Instead, it needs a negative membrane voltage to pass back to the Closed state.

When a sodium channel opens, it only stays that way briefly before going to an inactivated state. Recovery from inactivated back to "closed but openable" requires the

If you depolarize a cell gradually, this will open sodium channels, but it will also increase the number of channels stuck in this "inactivated" state. That means there are fewer channels available to flip from closed to open.

When a cell is hyperpolarized, there are fewer channels stuck in the inactivated state, and so the threshold potential can actually become more negative: it takes a smaller voltage step to open enough channels to trigger an action potential, because there are more channels available to open. You can describe this situation as being "more excitable" despite the hyperpolarized potential.

Some cells, including cardiac cells and other types of pacemaker neurons, will actually depolarize spontaneously from this hyperpolarized potential and reach threshold all on their own without external input.