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

ABSTRACT: OBJECTIVES:We examined whether two G protein-coupled receptors (GPCRs), muscarinic M1 receptors (M1Rs) and dopaminergic D2 receptors (D2Rs), utilize endogenously released fatty acid to inhibit L-type Ca2+ channels, CaV1.3. HEK-293 cells, stably transfected with M1Rs, were used to transiently transfect D2Rs and CaV1.3b with different CaV?-subunits, allowing for whole-cell current measurement from a pure channel population. RESULTS:M1R activation with Oxotremorine-M inhibited currents from CaV1.3b coexpressed with ?2?-1 and a ?1b, ?2a, ?3, or ?4-subunit. Surprisingly, the magnitude of inhibition was less with ?2a than with other CaV?-subunits. Normalizing currents revealed kinetic changes after modulation with ?1b, ?3, or ?4, but not ?2a-containing channels. We then examined if D2Rs modulate CaV1.3b when expressed with different CaV?-subunits. Stimulation with quinpirole produced little inhibition or kinetic changes for CaV1.3b coexpressed with ?2a or ?3. 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 CaV?-subunits could fine tune the response of Ca2+ influx following GPCR activation.

SUBMITTER: Roberts-Crowley ML

PROVIDER: S-EPMC6161362 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Roberts-Crowley Mandy L ML Rittenhouse Ann R AR

BMC research notes 20180927 1

<h4>Objectives</h4>We examined whether two G protein-coupled receptors (GPCRs), muscarinic M1 receptors (M1Rs) and dopaminergic D2 receptors (D2Rs), utilize endogenously released fatty acid to inhibit L-type Ca2+ channels, CaV1.3. HEK-293 cells, stably transfected with M1Rs, were used to transiently transfect D2Rs and CaV1.3b with different CaVβ-subunits, allowing for whole-cell current ...[more]

PMID: 30261922

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Dataset Information

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

Publications

Modulation of Ca<sub>V</sub>1.3b L-type calcium channels by M<sub>1</sub> muscarinic receptors varies with Ca<sub>V</sub>β subunit expression.

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