Dual activation of the cardiac Ca2+ channel α1C-subunit and its modulation by the β-subunit

Ca 2+ channels are heteromultimeric proteins in which the α 1 -subunit forms the voltage-dependent Ca 2+ -selective ionic channel. We reported recently that coexpression of the β-subunit with the cardiac α 1 -subunit (α 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 α 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 β-subunit potentiates Ca 2+ currents 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 α 1 -subunit and that the β-subunit increases Ca 2+ 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 α 1C also modulates the channel-gating behavior