Modulation of distinct isoforms of L-type calcium channels by Gq-coupled receptors in Xenopus oocytes: Antagonistic effects of Gβγ and protein kinase C

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Item Type:	Article
Title:	Modulation of distinct isoforms of L-type calcium channels by Gq-coupled receptors in Xenopus oocytes: Antagonistic effects of Gβγ and protein kinase C
Creators Name:	Weiss, S., Keren-Raifman, T., Oz, S., Ben Mocha, A., Haase, H. and Dascal, N.
Abstract:	L-type voltage dependent Ca (2+) channels (L-VDCCs; Cav 1.2) 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 {alpha} 1C, whereas known smooth muscle short-NT isoforms were inhibited by PKC and Gq activators. We report a novel regulation of the long-NT {alpha} 1C isoform by G{beta}{gamma}. G{beta}{gamma} inhibited whereas a G{beta}{gamma} scavenger protein augmented the Gq- but not phorbol ester - mediated enhancement of channel activity, suggesting that G{beta}{gamma} acts upstream from PKC. In vitro binding experiments reveal binding of both G{beta}{gamma} and PKC to {alpha} 1C-NT. However, PKC modulation was not altered by mutations of multiple potential phosphorylation cites in the NT, and was attenuated by a mutation of C-terminally located serine S1928. The insertion of exon 9a in intracelular loop 1 rendered the short-NT {alpha} 1C sensitive to PKC stimulation and to G{beta}{gamma} scavenging. Our results suggest a complex antagonistic interplay between Gq-activated PKC and G{beta}{gamma} in regulation of L-VDCC, in which multiple cytosolic segments of {alpha} 1C are involved.
Keywords:	Animals, Rabbits, Rats, Xenopus Laevis
Source:	Channels
ISSN:	1933-6950
Publisher:	Landes Bioscience
Volume:	6
Number:	6
Page Range:	426-437
Date:	1 November 2012
Official Publication:	https://doi.org/10.4161/chan.22016
PubMed:	View item in PubMed

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