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• W1575045803 abstract "L-type voltage dependent Ca2+ channels (L-VDCCs; Cav1.2) are crucial in cardiovascular physiology. In heart and smooth muscle, hormones and transmitters operating via Gq enhance L-VDCC currents via essential protein kinase C (PKC) involvement. Heterologous reconstitution studies in Xenopus oocytes suggested that PKC and Gq-coupled receptors increased L-VDCC currents only in cardiac long N-terminus (NT) isoforms of α1C, whereas known smooth muscle short-NT isoforms were inhibited by PKC and Gq activators. We report a novel regulation of the long-NT α1C isoform by Gβγ. Gβγ inhibited whereas a Gβγ scavenger protein augmented the Gq- but not phorbol ester-mediated enhancement of channel activity, suggesting that Gβγ acts upstream from PKC. In vitro binding experiments reveal binding of both Gβγ and PKC to α1C-NT. However, PKC modulation was not altered by mutations of multiple potential phosphorylation sites in the NT, and was attenuated by a mutation of C-terminally located serine S1928. The insertion of exon 9a in intracellular loop 1 rendered the short-NT α1C sensitive to PKC stimulation and to Gβγ scavenging. Our results suggest a complex antagonistic interplay between Gq-activated PKC and Gβγ in regulation of L-VDCC, in which multiple cytosolic segments of α1C are involved." @default.
• W1575045803 created "2016-06-24" @default.
• W1575045803 creator A5003047676 @default.
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• W1575045803 creator A5028895482 @default.
• W1575045803 creator A5054988954 @default.
• W1575045803 creator A5065750976 @default.
• W1575045803 date "2012-11-18" @default.
• W1575045803 modified "2023-09-30" @default.
• W1575045803 title "Modulation of distinct isoforms of L-type calcium channels by G_q-coupled receptors in Xenopus oocytes" @default.
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• W1575045803 doi "https://doi.org/10.4161/chan.22016" @default.
• W1575045803 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3536727" @default.
• W1575045803 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22990911" @default.
• W1575045803 hasPublicationYear "2012" @default.
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