Regulation of cloned cardiac L-type calcium channels by cGMP-dependent protein kinase

L. H. Jiang, D. J. Gawler, N. Hodson, C. J. Milligan, H. A. Pearson, V. Porter, D. Wray

    Research output: Contribution to journalArticlepeer-review

    Abstract

    We have studied the effect of 8-bromo-cyclic GMP (8-Br-cGMP) on cloned cardiac L-type calcium channel currents to determine the site and mechanism of action underlying the functional effect. Rabbit cardiac α(1C) subunit, in the presence or absence of β1 subunit (rabbit skeletal muscle) or β2 subunit (rat cardiac/brain), was expressed in Xenopus oocytes, and two- electrode voltage-clamp recordings were made 2 or 3 days later. Application of 8-Br-cGMP caused decreases in calcium channel currents in cells expressing the α(1C) subunit, whether or not a β subunit was co-expressed. No inhibition of currents by 8-Br-cGMP was observed in the presence of the protein kinase G inhibitor KT5823. Substitutions of serine residues by alanine were made at residues Ser533 and Ser1371 on the α(1C) subunit. As for wild type, the mutant S1371A exhibited inhibition of calcium channel currents by 8-Br-cGMP, whereas no effect of 8-Br-cGMP was observed for mutant S533A. Inhibition of calcium currents by 8-Br-cGMP was also observed in the additional presence of the α2δ subunit for wild type channels but not for the mutant S533A. These results indicate that cGMP causes inhibition of L-type calcium channel currents by phosphorylation of the α(1C) subunit at position Ser533 via the action of protein kinase G.
    Original languageEnglish
    Pages (from-to)6135-6143
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume275
    Issue number9
    DOIs
    Publication statusPublished - 3 Mar 2000

    Fingerprint

    Dive into the research topics of 'Regulation of cloned cardiac L-type calcium channels by cGMP-dependent protein kinase'. Together they form a unique fingerprint.

    Cite this