Regulation of Ca‐sensitive inactivation of a l‐type Ca2+ channel by specific domains of β subunits

Abstract

Ca²⁺ channel auxiliary β subunits have been shown to modulate voltage-dependent inactivation of various types of Ca²⁺ channels. The β₁ and β₂ subunits, that are differentially expressed with the L-type α₁ Ca²⁺ channel subunit in heart, muscle and brain, can specifically modulate the Ca²⁺-dependent inactivation kinetics. Their expression in Xenopus oocytes with the α_1C subunit leads, in both cases, to biphasic Ca²⁺ current decays, the second phase being markedly slowed by expression of the β₂ subunit. Using a series of β subunit deletion mutants and chimeric constructs of β₁ and β₂ subunits, we show that the inhibitory site located on the amino-terminal region of the β_2a subunit is the major element of this regulation. These results thus suggest that different splice variants of the β₂ subunit can modulate, in a specific way, the Ca²⁺ entry through L-type Ca²⁺ channels in different brain or heart regions.