Modulation of Ca(V)1.3b L-type calcium channels by M(1) muscarinic receptors varies with Ca(V)β subunit expression

OBJECTIVES: We examined whether two G protein-coupled receptors (GPCRs), muscarinic M(1) receptors (M(1)Rs) and dopaminergic D(2) receptors (D(2)Rs), utilize endogenously released fatty acid to inhibit L-type Ca(2+) channels, Ca(V)1.3. HEK-293 cells, stably transfected with M(1)Rs, were used to transiently transfect D(2)Rs and Ca(V)1.3b with different Ca(V)β-subunits, allowing for whole-cell current measurement from a pure channel population. RESULTS: M(1)R activation with Oxotremorine-M inhibited currents from Ca(V)1.3b coexpressed with α(2)δ-1 and a β(1b), β(2a), β(3), or β(4)-subunit. Surprisingly, the magnitude of inhibition was less with β(2a) than with other Ca(V)β-subunits. Normalizing currents revealed kinetic changes after modulation with β(1b), β(3), or β(4), but not β(2a)-containing channels. We then examined if D(2)Rs modulate Ca(V)1.3b when expressed with different Ca(V)β-subunits. Stimulation with quinpirole produced little inhibition or kinetic changes for Ca(V)1.3b coexpressed with β(2a) or β(3). However, quinpirole inhibited N-type Ca(2+) currents in a concentration-dependent manner, indicating functional expression of D(2)Rs. N-current inhibition by quinpirole was voltage-dependent and independent of phospholipase A(2) (PLA(2)), whereas a PLA(2) antagonist abolished M(1)R-mediated N-current inhibition. These findings highlight the specific regulation of Ca(2+) channels by different GPCRs. Moreover, tissue-specific and/or cellular localization of Ca(V)1.3b with different Ca(V)β-subunits could fine tune the response of Ca(2+) influx following GPCR activation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3783-x) contains supplementary material, which is available to authorized users.