Modal behavior of the μ1 Na⁺ channel and effects of coexpression of the β₁-subunit

The adult rat skeletal muscle Na⁺ channel α-subunit (μ1) appears to gate modally with two kinetic schemes when the channel is expressed in Xenopus oocytes. In the fast mode μ1 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 β₁ reduces slow-mode gating, so that channels gate almost exclusively in the fast mode. Analysis of open-time histograms showed that μ1 and μ1 + β₁ 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 β₁ was coexpressed with μ1 in oocytes, the long MOT fraction was greatly reduced. It appears that although μ1 and μ1 + β₁ share the same two open states, the β₁-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 β₁. Experiments also showed that the rate of activation for the fast mode of μ1 is identical to that for μ1 + β₁ and is thus more rapid than the rate of activation for the slow mode. It can be concluded that β₁ restores native-like kinetics in μ1 by favoring the fast-gating mode.