THE BETA-SUBUNIT CONTROLS THE GATING AND DIHYDROPYRIDINE SENSITIVITY OF THE SKELETAL-MUSCLE CA-2+ CHANNEL

The skeletal muscle (SKM) L-type Ca2+ channel is composed of a central subunit designated alpha1, which contains the pore and the dihydropyridine (DHP) binding domains and three associated subunits, alpha2/delta, beta and gamma, which influence the activity of the SKMalpha1. Coexpression of SKMalpha1 and SKMbeta in stably transfected mouse L cells results in a dramatic increase in DHP binding accompanied by fast gated Ba2+ currents. We report here that this "SKMalpha1beta-related phenotype" can be converted upon intracellular trypsin treatment into a slowly inactivating, DHP sensitive "SKMalpha1 phenotype." These observations indicate that current amplitude, fast inactivation, and DHP sensitivity are modulated by an interaction of SKMalpha1 and SKMbeta on the internal side of the membrane.