© 2000 American Heart Association, Inc.
Review |
Regulation of Cardiac L-Type Calcium Channels by Protein Kinase A and Protein Kinase C
From the Departments of Medicine (T.J.K.), Physiology (T.J.K.), and Pharmacology (J.W.H.), University of Wisconsin, Madison, Wis.
Correspondence to Dr Timothy J. Kamp, University of Wisconsin–Madison, H6/343 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3248. E-mail tjk{at}medicine.wisc.edu
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.
ß-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 
1C
(Cav1.2) subunit. Both
1C and ß2a 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 1C
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.
Key Words: L-type calcium channel • protein kinase C • protein kinase A • heart • regulation • phosphorylation
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