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Sci. Signal., 28 September 2010
Vol. 3, Issue 141, p. pe33
[DOI: 10.1126/scisignal.3141pe33]


β-Adrenergic Regulation of the L-Type Ca2+ Channel CaV1.2 by PKA Rekindles Excitement

Johannes W. Hell*

Department of Pharmacology, University of California, Davis, CA 95615, USA.

Abstract: When we are frightened, our hearts beat more rapidly and forcefully so we can fight more intensely or run away faster. This fight-or-flight response is triggered by the release of norepinephrine from neurons of the sympathetic nervous system. Norepinephrine activates the classic β-adrenergic receptor–heterotrimeric Gs protein–adenylyl cyclase–adenosine 3',5'-monophosphate–protein kinase A (PKA) signaling cascade. One of the main PKA targets implicated in this response is the L-type Ca2+ channel CaV1.2, which mediates Ca2+ influx into cardiomyocytes. Because of its central function in regulating heartbeat, and because the underlying molecular mechanism has remained elusive, understanding the regulation of CaV1.2 has been considered the holy grail for the field of channel regulation. New evidence from the quest to solve the mystery of CaV1.2 regulation has revealed that reproducible reconstitution of this regulation in heterologous cells requires a perfect balance of the ratio of CaV1.2 to A-kinase anchor proteins (AKAPs). Proteolytic processing of the cytosolic C terminus of the central, pore-forming {alpha}11.2 subunit of CaV1.2 contributed to its regulation by PKA, and Ser1700 in the C terminus of the {alpha}11.2 subunit emerged as the relevant PKA phosphorylation site.

* Corresponding author. E-mail, jwhell{at}

Citation: J. W. Hell, β-Adrenergic Regulation of the L-Type Ca2+ Channel CaV1.2 by PKA Rekindles Excitement. Sci. Signal. 3, pe33 (2010).

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A-kinase anchoring proteins: scaffolding proteins in the heart.
D. Diviani, K. L. Dodge-Kafka, J. Li, and M. S. Kapiloff (2011)
Am J Physiol Heart Circ Physiol 301, H1742-H1753
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