The Ca 2+ channel subunit Ca V β2a down-regulates voltage-activated ion current densities by disrupting actin-dependent traffic in chromaffin cells.

beta-Subunits of the Ca2+ channel have been conventionally regarded as auxiliary subunits that regulate the expression and activity of the pore-forming alpha(1) subunit. However, they comprise protein-protein interaction domains, such as a SRC homology 3 domain (SH3) domain, which make them potential signaling molecules. Here we evaluated the role of the beta 2a subunit of the Ca2+ channels (Ca-V beta 2a) and its SH3 domain (beta 2a-SH3) in late stages of channel trafficking in bovine adrenal chromaffin cells. Cultured bovine adrenal chromaffin cells were injected with Ca-V beta 2a or beta 2a-SH3 under different conditions, in order to acutely interfere with endogenous associations of these proteins. As assayed by whole-cell patch clamp recordings, Ca2+ currents were reduced by Ca-V beta 2a in the presence of exogenous alpha 1-interaction domain. beta 2a-SH3, but not its dimerization-deficient mutant, also reduced Ca2+ currents. Na+ currents were also diminished following beta 2a-SH3 injection. Furthermore, beta 2a-SH3 was still able to reduce Ca2+ currents when dynamin-2 function was disrupted, but not when SNARE-dependent exocytosis or actin polymerization was inhibited. Together with the additional finding that both Ca-V beta 2a and beta 2a-SH3 diminished the incorporation of new actin monomers to cortical actin filaments, beta 2a-SH3 emerges as a signaling module that might down-regulate forward trafficking of ion channels by modulating actin dynamics.