Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C

Timothy J. Kamp, Johannes W Hell

Research output: Contribution to journalArticle

447 Scopus citations

Abstract

Voltage-dependent L-type Ca2+ channels are multisubunit transmembrane proteins, which allow the influx of Ca2+ (I(Ca)) essential for normal excitability and excitation-contraction coupling in cardiac myocytes. A variety of different receptors and signaling pathways provide dynamic regulation of I(Ca) in the intact heart. The present review focuses on recent evidence describing the molecular details of regulation of L-type Ca2+ channels by protein kinase A (PKA) and protein kinase C (PKC) pathways. Multiple G protein-coupled receptors act through cAMP/PKA pathways to regulate L-type channels. β-Adrenergic receptor stimulation results in a marked increase in I(Ca), which is mediated by a cAMP/PKA pathway. Growing evidence points to an important role of localized signaling complexes involved in the PKA-mediated regulation of I(Ca), including A-kinase anchor proteins and binding of phosphatase PP2a to the carboxyl terminus of the α(1C) (Ca(v)1.2) subunit. Both α(1C) and β(2a) subunits of the channel are substrates for PKA in vivo. The regulation of L-type Ca2+ channels by Gq-linked receptors and associated PKC activation is complex, with both stimulation and inhibition of I(Ca) being observed. The amino terminus of the α(1C) subunit is critically involved in PKC regulation. Crosstalk between PKA and PKC pathways occurs in the modulation of I(Ca). Ultimately, precise regulation of I(Ca) is needed for normal cardiac function, and alterations in these regulatory pathways may prove important in heart disease.

Original languageEnglish (US)
Pages (from-to)1095-1102
Number of pages8
JournalCirculation Research
Volume87
Issue number12
StatePublished - Dec 8 2000
Externally publishedYes

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Keywords

  • Heart
  • L-type calcium channel
  • Phosphorylation
  • Protein kinase A
  • Protein kinase C
  • Regulation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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