minimovie on Neurons in action 1.5

[biology455]

I have a question about the minimovie in version 1.5 that shows the blocking of the voltage-gated K+ channel. I am assuming that the minimovie shows a block in voltage-gated K+ channels but that the inactivation of the voltage-gated Na+ channel is not taken into account.

However given that there are no voltage-gated K+ channels at the mammalian node of Ranvier in peripheral nerves and that the AP repolarizes solely due to Na+ channel inactivation I don't think this movie is a very good demonstration of AP dynamics. Is there an alternative movie to be used to show what happens when the K+ channels are block and as well taking into consideration Na+ channel inactivation?

Thanks..

[john moore]

The differences between frog and mammalian node channel densities are discussed in the experimental observations link in the Myelinated Axon Tutorial. The simulations were done for the frog axon.

The simulations included the inactivation of the Na channels and can be seen in the Minimovie entitled "Blocking the K Channels: View the Conductances." Notice that even though the Na channels inactivate and the Na conductance decreases dramatically, the voltage stays near ENa, declining slowly due to the leak conductance.

[biology455]

So in the minimovie the K+ channel conductance is blocked and yet the voltage-gated Na+ channels STILL inactivate? Then why stay at ENa? There is no longer any more Na+ conductance due to the channels being inactivated, PNa+ would be back to resting levels in the absence of Na+ conductance and the membrane potential would fall back to rest. Na+ inactivation is within milliseconds and so why the very long plateau at ENa+? That makes no sense. Experimentally in the mammalian nerve if you blockvoltage-gated K+ channels with TEA in non-myelinated axons you still get rapid repolarization to rest within milliseconds due to the lack of Na+ conductance and the presence of the leak channels (Belluzzi and Sacchi, 1991). Is the leak channel so minor a component in the frog nerve compared to mammalian? What happens if you model a mammalian non-myelinated nerve does the membrane potential still plateau for as long as in the frog? If so then I am guessing that the conductances need to be corrected. Anyway the minimovie certainly doesn't work in the teaching of mammalian nerves.

[john moore]

The patch minimovies are made for isolated patches with simulations of the Hodgkin-Huxley equations and only include the standard HH Na, K, and leakage channels along with the membrane capacitance. When the K channels are blocked, and the membrane is only permeable to Na, the voltage will go to ENa. Because the membrane is so depolarized, now all of the Na channels will inactivate and the only open channels remaining will be the leak channels. Thus, with time, Vm will go to Eleak.

As for mammalian non-myelinated nerve, the Belluzzi and Sacchi paper that you quote lists three different K channels in that axon. We are not familiar with the details of this paper and the relative sensitivities of these conductances to TEA but presumably the repolarization is due to one or more of the channels being insensitive to TEA and still available to repolarize the axon. You are correct that the minimovie teaches principles rather than exact conditions for particular axons. Even amongst mammalian axons there would be variability in the particular channel types and their pharmacology. Our aim was to teach principles and the minimovies were designed only as an introduction to the basic physiology of nerve function.

Thanks for your interest in NIA. I hope you can use the movies anyway and progress from there to showing your students the complications of adding more channels to a patch or an axon.