Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response

被引:41
作者
Catterall, William A. [1 ]
机构
[1] Univ Washington, Dept Pharmacol, Box 357280, Seattle, WA 98195 USA
关键词
A Kinase Anchoring Protein; beta-adrenergic; calcium channel; cAMP-dependent protein kinase; cardiac hypertrophy; Cav1.2; heart failure; L-type calcium current; DEPENDENT PROTEIN-KINASE; BETA-ADRENERGIC REGULATION; SKELETAL-MUSCLE FIBERS; SLOW INWARD CURRENT; FULL-LENGTH FORM; 2 SIZE FORMS; CA2+ CHANNEL; CYCLIC-AMP; CARBOXYL-TERMINUS; ALPHA-1; SUBUNIT;
D O I
10.2174/1874467208666150507103417
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Intracellular calcium transients generated by activation of voltage-gated calcium (CaV) channels generate local signals, which initiate physiological processes such as secretion, synaptic transmission, and excitation-contraction coupling. Regulation of calcium entry through CaV channels is crucial for control of these physiological processes. In this article, I review experimental results that have emerged over several years showing that cardiac Ca(V)1.2 channels form a local signaling complex, in which their proteolytically processed distal C-terminal domain, an A-Kinase Anchoring Protein, and cyclic AMP-dependent protein kinase (PKA) interact directly with the transmembrane core of the ion channel through the proximal C-terminal domain. This signaling complex is the substrate for beta-adrenergic up-regulation of the Ca(V)1.2 channel in the heart during the fight-or-flight response. Protein phosphorylation of two sites at the interface between the distal and proximal C-terminal domains contributes importantly to control of basal Ca(V)1.2 channel activity, and phosphorylation of Ser1700 by PKA at that interface up-regulates Ca(V)1.2 activity in response to beta-adrenergic signaling. Thus, the intracellular C-terminal domain of Ca(V)1.2 channels serves as a signaling platform, mediating beat-to-beat physiological regulation of channel activity and up-regulation by beta-adrenergic signaling in the fight-or-flight response.
引用
收藏
页码:12 / 21
页数:10
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