EFFECT OF BAY-K-8644 (-) AND THE BETA(2A) SUBUNIT ON CA2-DEPENDENT INACTIVATION IN ALPHA(1C) CA2+ CHANNELS()

Ca2+ currents recorded from Xenopus oocytes expressing only the alpha( 1c) pore-forming subunit of the cardiac Ca2+ channel show Ca2+-depende nt inactivation with a single exponential decay. This current-dependen t inactivation is not detected for inward Ba2+ currents in external Ba 2+. Facilitation of pore opening speeds up the Ca2+-dependent inactiva tion process and makes evident an initial fast rate of decay. Facilita tion can be achieved by (a) coexpression of the beta(2A) subunit with the alpha(1c) subunit, or (b) addition of saturating Bay K 8644 (-) co ncentration to alpha(1c) channels. The addition of Bay K 8644 (-) to a lpha(1c)beta(2a) channels makes both rates of inactivation faster. All these maneuvers do not induce inactivation in Ba2+ currents in our ex pression system. These results support the hypothesis of a mechanism f or the Ca2+-dependent inactivation process that is sensitive to both C a2+ flux (single channel amplitude) and open probability. We conclude that the Ca2+ site for inactivation is in the alpha(1c) pore-forming s ubunit and we propose a kinetic model to account for the main features of alpha(1c)beta(2a) Ca2+ currents.