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.