Effect of Bay K 8644 (−) and the β(2a) Subunit on Ca(2+)-dependent Inactivation in α(1C) Ca(2+) Channels

Ca(2+) currents recorded from Xenopus oocytes expressing only the α(1C) pore-forming subunit of the cardiac Ca(2+) channel show Ca(2+)-dependent inactivation with a single exponential decay. This current-dependent inactivation is not detected for inward Ba(2+) currents in external Ba(2+). Facilitation of pore opening speeds up the Ca(2+)-dependent inactivation process and makes evident an initial fast rate of decay. Facilitation can be achieved by (a) coexpression of the β(2a) subunit with the α(1C) subunit, or (b) addition of saturating Bay K 8644 (−) concentration to α(1C) channels. The addition of Bay K 8644 (−) to α(1C)β(2a) channels makes both rates of inactivation faster. All these maneuvers do not induce inactivation in Ba(2+) currents in our expression system. These results support the hypothesis of a mechanism for the Ca(2+)-dependent inactivation process that is sensitive to both Ca(2+) flux (single channel amplitude) and open probability. We conclude that the Ca(2+) site for inactivation is in the α(1C) pore-forming subunit and we propose a kinetic model to account for the main features of α(1C)β(2a) Ca(2+) currents.