DUAL ACTIVATION OF THE CARDIAC CA2+ CHANNEL ALPHA(1C)-SUBUNIT AND ITS MODULATION BY THE BETA-SUBUNIT

Ca2+ channels are heteromultimeric proteins in which the alpha(1)-subunit forms the voltage-dependent Ca2+-selective ionic channel. We reported recently that coexpression of the beta-subunit with the cardiac alpha-subunit (alpha(1C)) facilitates channel opening without affecting either the amplitude or the time course of the gating currents (13). Here we present evidence for the existence of two modes of channel opening. Xenopus oocytes expressing the alpha(1C)-subunit alone display two modes of activation as indicated by the double-exponential time course of macroscopic ionic currents and the two open-time distributions of single channels. Coexpression of the beta-subunit potentiates Ca2+ cut-rents by a relative increase of the fast-activating component, an acceleration of the slow component, and a larger proportion of long openings. We propose that multiple modes of gating are encoded in the alpha 1-subunit and that the beta-subunit increases Ca2+ channel opening by favoring a willing mode of gating in which the final transitions leading to channel opening are facilitated. In addition, we show that the carboxy terminus of ale also modulates the channel-gating behavior.