Thread: How is Na+ inactivation possible in a voltage-clamp experiment?

Hi Everyone,

Okay I have a burning question, and no matter how many equations I seem to encounter and complex explanations, I cannot figure out the following: How is Na+ inactivation possible in a voltage-clamp experiment? I am confused because inactivation gates are VOLTAGE-DEPENDENT, and if your voltage is clamped at say -20mV (enough for depolarization but not enough for inactivation gates to close under normal circumstances), then how do these inactivation gates close?

Thank you so much! I really appreciate any help you can provide.

-Nicole

Hi Nicole-
I think I might be able to explain. As I understand it, voltage-dependent Na+ channels have this ball-and-chain length of protein hanging off the internal size of the receptor. At resting potential, when the receptor is closed, it's extended and just hanging out in the cytoplasm. After the cell hits threshold and the channel opens, the ball begins to swing up and close the channel. It takes a millisecond or two- long enough for Na+ to rush in and continue to propagate the action potential- but then the ball plugs up the channel. For as long as the channel is open (that is, as long as the cell remains above threshold), it'll keep clogging up the pore. However, when things drop back down to resting and the channel "closes" (the pore itself), the ball will swing back out and we start the whole thing over again.

So when the cell is clamped to -20mV, the channel will open briefly but then get plugged up by this ball-and-chain, which stays in place for as long as we keep things at that voltage.

I think I heard about an experiment that actually cut all the "chains", leaving the balls free-floating, and the whole system still worked.

Hope that helped,
wick