Modulation of CaV1.3b L-type calcium channels by M1 muscarinic receptors varies with CaVβ subunit expression
Year: 2018
Type: article
Abstract: 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. 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.
Source: BMC Research Notes
Institution: University of Massachusetts Chan Medical School
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,690
OpenAlex ID: W2894465718