Molecular and genetic basis of sudden cardiac death
Alfred L. George Jr.
Alfred L. George Jr.
Published January 2, 2013
Citation Information: J Clin Invest. 2013;123(1):75-83. https://doi.org/10.1172/JCI62928.
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Review Series

Molecular and genetic basis of sudden cardiac death

Abstract

The abrupt cessation of effective cardiac function due to an aberrant heart rhythm can cause sudden and unexpected death at any age, a syndrome called sudden cardiac death (SCD). Annually, more than 300,000 cases of SCD occur in the United States alone, making this a major public health concern. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of heart rhythm. This knowledge has helped shape the current diagnosis and treatment of inherited arrhythmia susceptibility syndromes associated with SCD and has provided a pathophysiological framework for understanding more complex conditions predisposing to this tragic event. This Review presents an overview of the molecular basis of SCD, with a focus on monogenic arrhythmia syndromes.

Authors

Alfred L. George Jr.

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Figure 4

Molecular basis for intracellular Ca2+ homeostasis.

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Molecular basis for intracellular Ca2+ homeostasis. Illustration of T ...
Illustration of T tubule with adjacent junctional SR containing the ryanodine receptor (RYR2) Ca2+ release channel, calsequestrin Ca2+ binding protein, and Ca2+ pump (SERCA) with regulatory protein phospholamban (PLN). The electrogenic NCX is represented on the surface plasma membrane. Electrical impulses conducted into the T tubules trigger a wave of Ca2+ influx via the voltage-dependent, L-type Ca2+ channel (LTCC) that promotes Ca2+ release through RYR2. This release of Ca2+ from the SR promotes myocyte contraction. The subsequent removal of cytosolic Ca2+, mostly by reuptake into the SR by SERCA and by pumping out of the cell by the plasma membrane Ca2+ ATPase (PMCA), and the exchange for extracellular Na+ by an electrogenic NCX on the plasma membrane, terminates the contraction.