MECHANISM OF MODULATION OF SINGLE SODIUM-CHANNELS FROM SKELETAL-MUSCLE BY THE BETA(1)-SUBUNIT FROM RAT-BRAIN

We studied the molecular mechanism of the rat skeletal muscle alpha-subunit (alpha(mu I)) gating kinetics modulation by the brain beta(1)-subunit by heterologous expression of single sodium channels from alpha(mu I) and beta(1) in Xenopus laevis oocytes. Coexpression of beta(1) reduced mean open time at -10 mV to similar to 21% when compared to channels expressed by alpha(mu I) alone. Channels formed by alpha(mu I) exerted multiple openings per depolarization, which occurred in bursts, in contrast to the channels formed by the alpha(mu I)/beta(1) complex that opened in average only once per depolarizing voltage pulse. Macroscopic current decay (mcd), as evidenced by reconstructed open probability vs. time (p(o(t))), was greatly accelerated by beta(1), closely resembling mcd of sodium currents from native skeletal muscle. Generally p(o(t)), was larger for channels expressed from the pure alpha(mu I) subunit. From our single channel data we conclude that beta(1) accelerates the inactivation process of the sodium channel complex.