Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia

Andrew R. Marks, Silvia Priori, Mirella Memmi, Kimmo Kontula, Päivi J. Laitinen

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

The cardiac ryanodine receptor (RyR2), the major calcium release channel on the sarcoplasmic reticulum (SR) in cardiomyocytes, has recently been shown to be involved in at least two forms of sudden cardiac death (SCD): (1) Catecholaminergic polymorphic ventricular tachycardia (CPVT) or familial po[ymorphic VT (FPVT); and (2) Arrhythmogenic right ventricular dysplasia type 2 (ARVD2). Eleven RyR2 missense mutations have been linked to these diseases. All eteven RyR2 mutations cluster into 3 regions of RyR2 that are homologous to the three malignant hyperthermia (MH)/central core disease (CCD) mutation regions of the skeletal muscle ryanodine receptor/calcium release channel RyR1. MH/CCD RyR1 mutations have been shown to alter calcium-induced calcium release. Sympathetic nervous system stimulation leads to phosphorylation of RyR2 by protein kinase A (PKA). PKA phosphorylation of RyR2 activates the channel. In conditions associated with high rates of SCD such as heart failure RyR2 is PKA hyperphosphorylated resulting in "leaky" channels. SR calcium leak during diastole can generate "delayed after depolarizations" that can trigger fatal cardiac arrhythmias (e.g., VT). we propose that RyR2 mutations linked to genetic forms of catecholaminergic-induced SCD may alter the regulation of the channel resulting in increased SR calcium leak during sympathetic stimulation.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalJournal of Cellular Physiology
Volume190
Issue number1
DOIs
Publication statusPublished - 2002

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Ryanodine Receptor Calcium Release Channel
Calcium
Sudden Cardiac Death
Sarcoplasmic Reticulum
Central Core Myopathy
Cyclic AMP-Dependent Protein Kinases
Malignant Hyperthermia
Mutation
Phosphorylation
Polymorphic catecholergic ventricular tachycardia
Arrhythmogenic Right Ventricular Dysplasia
Diastole
Sympathetic Nervous System
Depolarization
Neurology
Missense Mutation
Calcium Channels
Cardiac Myocytes
Muscle
Cardiac Arrhythmias

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia. / Marks, Andrew R.; Priori, Silvia; Memmi, Mirella; Kontula, Kimmo; Laitinen, Päivi J.

In: Journal of Cellular Physiology, Vol. 190, No. 1, 2002, p. 1-6.

Research output: Contribution to journalArticle

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