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

TJ Kamp, JW Hell - Circulation research, 2000 - Am Heart Assoc
TJ Kamp, JW Hell
Circulation research, 2000Am Heart Assoc
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 …
Abstract
—Voltage-dependent L-type Ca2+ channels are multisubunit transmembrane proteins, which allow the influx of Ca2+ (ICa) essential for normal excitability and excitation-contraction coupling in cardiac myocytes. A variety of different receptors and signaling pathways provide dynamic regulation of ICa 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 ICa, 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 ICa, including A-kinase anchor proteins and binding of phosphatase PP2a to the carboxyl terminus of the α1C (Cav1.2) subunit. Both α1C and β2a 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 ICa being observed. The amino terminus of the α1C subunit is critically involved in PKC regulation. Crosstalk between PKA and PKC pathways occurs in the modulation of ICa. Ultimately, precise regulation of ICa is needed for normal cardiac function, and alterations in these regulatory pathways may prove important in heart disease.
Am Heart Assoc