期刊
CIRCULATION RESEARCH
卷 87, 期 12, 页码 1095-1102出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.87.12.1095
关键词
L-type calcium channel; protein kinase C; protein kinase A; heart; regulation; phosphorylation
资金
- NHLBI NIH HHS [P01 HL47053, R01 HL59429, R01 HL61537] Funding Source: Medline
Voltage-dependent L-type Ca2+ channels Lire 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-typr channels. beta -Adrenerlic 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 alpha (1C) (Ca(v)1.2) Subunit. Both alpha (1C) and beta (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 alpha (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.
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