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ELECTROPHYSIOLOGY

Cardiac Ca2+ current is ‘Rad’-ically altered by adrenergic activation

Nature Cardiovascular Research volume 1, pages 980–981 (2022)Cite this article

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The rapid enhancement of cardiac Ca2+ current (ICa,L) is central to enhanced heart function during the sympathetic fight-or-flight response. A new study shows how the small GTPase Rad mediates tonic ICa,L inhibition that is relieved after PKA-dependent phosphorylation of Rad, which causes release of Rad from the Ca2+ channel and increased ICa,L.

The β-adrenergic receptor (β-AR)-induced increase in L-type Ca2+ current (ICa,L) in cardiac myocytes is a cornerstone of the sympathetic cardiac fight-or-flight response by which cardiac myocyte Ca2+ transients and contraction are increased1. A previous study identified the monomeric G protein Rad as the crucial missing link in the molecular understanding of the large increase in ICa,L in cardiac myocytes that is caused by β-AR and protein kinase A (PKA) activation2.

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Fig. 1: Model for cardiac ICa,L regulation by β-AR signaling involving Rad.

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

    Donald M. Bers

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  1. Donald M. Bers
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Correspondence to Donald M. Bers.

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Bers, D.M. Cardiac Ca2+ current is ‘Rad’-ically altered by adrenergic activation. Nat Cardiovasc Res 1, 980–981 (2022). https://doi.org/10.1038/s44161-022-00163-0

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