Published:
Proceedings of the National Academy of Sciences, 2021
Published in:
Proceedings of the National Academy of Sciences, 118 (2021) 21
Language:
English
DOI:
10.1073/pnas.2100021118
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
Significance The strengthening of heart contraction by epinephrine (adrenaline) and norepinephrine starts with the activation of β-adrenergic receptors and culminates in a protein kinase A–mediated increase in Ca 2+ influx through the voltage-gated Ca 2+ channel, Ca V 1.2, into cardiomyocytes. Many crucial molecular details of this vital physiological regulation remained enigmatic for decades, not the least owing to the difficulty of reconstituting the regulation in model cells. Capitalizing on the recent discovery of the central role of the Ca V 1.2-associated protein, Rad, we present a report of full reconstitution of the β-AR–Ca V 1.2 cascade in a model system, the Xenopus oocyte, and investigate crucial aspects of regulation such as the roles of auxiliary subunits and diverse forms of the channel protein.