A β4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel α(1A) subunit

Abstract

The voltage-gated calcium channel β subunit is a cytoplasmic protein that stimulates activity of the channel-forming subunit, α1, in several ways. Complementary binding sites on α1 and β have been identified that are highly conserved among isoforms of the two subunits, but this interaction alone does not account for all of the functional effects of the β subunit. We describe here the characterization in vitro of a second interaction, involving the carboxyl-terminal cytoplasmic domain of α(1A) and showing specificity for the β4 (and to a lesser extent β(2a)) isoform. A deletion and chimera approach showed that the carboxyl-terminal region of β4, poorly conserved between β isoforms, contains the interaction site and plays a role in the regulation of channel inactivation kinetics. This is the first demonstration of a molecular basis for the specificity of functional effects seen for different combinations of these two channel components.