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

β-Subunits of the Ca channel have been conventionally regarded as auxiliary subunits that regulate the expression and activity of the pore-forming α 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 β2a subunit of the Ca channels (Ca β2a) and its SH3 domain (β2a-SH3) in late stages of channel trafficking in bovine adrenal chromaffin cells. Cultured bovine adrenal chromaffin cells were injected with Ca β2a or β2a-SH3 under different conditions, in order to acutely interfere with endogenous associations of these proteins. As assayed by whole-cell patch clamp recordings, Ca currents were reduced by Ca β2a in the presence of exogenous α1-interaction domain. β2a-SH3, but not its dimerization-deficient mutant, also reduced Ca currents. Na currents were also diminished following β2a-SH3 injection. Furthermore, β2a-SH3 was still able to reduce Ca 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 β2a and β2a-SH3 diminished the incorporation of new actin monomers to cortical actin filaments, β2a-SH3 emerges as a signaling module that might down-regulate forward trafficking of ion channels by modulating actin dynamics.