Modal behavior of the mu 1 Na+ channel and effects of coexpression of the beta 1-subunit.

The adult rat skeletal muscle Na+ channel alpha-subunit (mu 1) appears to gate modally with two kinetic schemes when the channel is expressed in Xenopus oocytes. In the fast mode mu 1 single channels open only once or twice per depolarizing pulse, but in the slow mode the channels demonstrate bursting behavior. Slow-mode gating was favored by hyperpolarized holding potentials and slow depolarizing rates, whereas fast-mode gating was favored by depolarized holding potentials and rapid depolarizations. Single-channel studies showed that coexpression of beta 1 reduces slow-mode gating, so that channels gate almost exclusively in the fast mode. Analysis of open-time histograms showed that mu 1 and mu 1 + beta 1 both have two open-time populations with the same mean open times (MOTs). The difference lies in the relative sizes of the long and short MOT components. When beta 1 was coexpressed with mu 1 in oocytes, the long MOT fraction was greatly reduced. It appears that although mu 1 and mu 1 + beta 1 share the same two open states, the beta 1-subunit favors the mode with the shorter open state. Examination of first latencies showed that it is likely that the rate of activation is increased upon coexpression with beta 1. Experiments also showed that the rate of activation for the fast mode of mu 1 is identical to that for mu 1 + beta 1 and is thus more rapid than the rate of activation for the slow mode. It can be concluded that beta 1 restores native-like kinetics in mu 1 by favoring the fast-gating mode.