Modulation of CaV1.3b L-type calcium channels by M1 muscarinic receptors varies with CaVβ subunit expression.

M1R activation with Oxotremorine-M inhibited currents from CaV1.3b coexpressed with α2δ-1 and a β1b, β2a, β3, or β4-subunit. Surprisingly, the magnitude of inhibition was less with β2a than with other CaVβ-subunits. Normalizing currents revealed kinetic changes after modulation with β1b, β3, or β4, but not β2a-containing channels. We then examined if D2Rs modulate CaV1.3b when expressed with different CaVβ-subunits. Stimulation with quinpirole produced little inhibition or kinetic changes for CaV1.3b coexpressed with β2a or β3. However, quinpirole inhibited N-type Ca2+ currents in a concentration-dependent manner, indicating functional expression of D2Rs. N-current inhibition by quinpirole was voltage-dependent and independent of phospholipase A2 (PLA2), whereas a PLA2 antagonist abolished M1R-mediated N-current inhibition. These findings highlight the specific regulation of Ca2+ channels by different GPCRs. Moreover, tissue-specific and/or cellular localization of CaV1.3b with different CaVβ-subunits could fine tune the response of Ca2+ influx following GPCR activation.