β-adrenergic regulation of the L-type Ca2+ channel Ca V1.2 by PKA rekindles excitement

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 α11.2 subunit of CaV1.2 contributed to its regulation by PKA, and Ser 1700 in the C terminus of the α11.2 subunit emerged as the relevant PKA phosphorylation site.

Original languageEnglish (US)
Article numberpe33
JournalScience Signaling
Volume3
Issue number141
DOIs
StatePublished - Sep 28 2010

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Cyclic AMP-Dependent Protein Kinases
Adrenergic Agents
A Kinase Anchor Proteins
Norepinephrine
Phosphorylation
Sympathetic Nervous System
Neurology
Adenylyl Cyclases
Cardiac Myocytes
Adenosine
Adrenergic Receptors
Neurons
Processing
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

β-adrenergic regulation of the L-type Ca2+ channel Ca V1.2 by PKA rekindles excitement. / Hell, Johannes W.

In: Science Signaling, Vol. 3, No. 141, pe33, 28.09.2010.

Research output: Contribution to journalArticle

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