Adrenergic Regulation of Calcium Channels in the Heart

Each heartbeat is initiated by the action potential, an electrical signal that depolarizes the plasma membrane and activates a cycle of calcium influx via voltage-gated calcium channels, calcium release via ryanodine receptors, and calcium reuptake and efflux via calcium-ATPase pumps and sodium-calc...

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Bibliographic Details
Published in:Annual review of physiology Vol. 84; p. 285
Main Authors: Papa, Arianne, Kushner, Jared, Marx, Steven O
Format: Journal Article
Language:English
Published: United States 10.02.2022
Subjects:
Adrenergic Agents - metabolism
Adrenergic Agents - pharmacology
Calcium - metabolism
Calcium Channels, L-Type - metabolism
Calcium Channels, L-Type - pharmacology
Humans
Myocardial Contraction - physiology
Myocytes, Cardiac - physiology
Ryanodine Receptor Calcium Release Channel - metabolism
Ryanodine Receptor Calcium Release Channel - pharmacology
calcium channel
excitation-contraction coupling
phosphorylation
sympathetic nervous system
heart
ISSN:1545-1585, 1545-1585
Online Access:Get more information
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Summary:Each heartbeat is initiated by the action potential, an electrical signal that depolarizes the plasma membrane and activates a cycle of calcium influx via voltage-gated calcium channels, calcium release via ryanodine receptors, and calcium reuptake and efflux via calcium-ATPase pumps and sodium-calcium exchangers. Agonists of the sympathetic nervous system bind to adrenergic receptors in cardiomyocytes, which, via cascading signal transduction pathways and protein kinase A (PKA), increase the heart rate (chronotropy), the strength of myocardial contraction (inotropy), and the rate of myocardial relaxation (lusitropy). These effects correlate with increased intracellular concentration of calcium, which is required for the augmentation of cardiomyocyte contraction. Despite extensive investigations, the molecular mechanisms underlying sympathetic nervous system regulation of calcium influx in cardiomyocytes have remained elusive over the last 40 years. Recent studies have uncovered the mechanisms underlying this fundamental biologic process, namely that PKA phosphorylates a calcium channel inhibitor, Rad, thereby releasing inhibition and increasing calcium influx. Here, we describe an updated model for how signals from adrenergic agonists are transduced to stimulate calcium influx and contractility in the heart.
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ISSN:1545-1585
1545-1585
DOI:10.1146/annurev-physiol-060121-041653