Calcium Store Stability as an Antiarrhythmic Endpoint

Title:Calcium Store Stability as an Antiarrhythmic Endpoint

Volume: 21 Issue: 8

Author(s): Antonio Zaza and Marcella Rocchetti

Affiliation:

Keywords: Alternans, antiarrhythmic therapy, DADs, EADs, intracellular Ca²⁺, RyRs, SERCA.

Abstract: Cardiac arrhythmias are electrical phenomena; thus, sarcolemmal ion channels have long been considered as targets of antiarrhythmic therapy. The contribution of abnormal intracellular Ca²⁺ handling to digitalis-induced arrhythmogenesis is an old concept; however, the role of abnormal Ca²⁺ handling as a common cause of arrhythmia, i.e. relevant to all arrhythmogenic mechanisms, has been fully recognized in more recent times. Stability of the intracellular Ca²⁺ store (sarcoplasmic reticulum, SR) is crucial to physiological Ca²⁺ handling; when it is compromised, Ca²⁺ may be released independently from excitation and lead to secondary perturbation of membrane potential. Ca²⁺ store stability depends on the interplay between sarcolemmal and SR “effectors” (ion channels and transports), which are mutually linked by Ca²⁺-mediated feed-back control. While instrumental to cell homeostasis, such control makes any attempt to modulate SR stability dauntingly complex. This review discusses current knowledge on the factors leading to SR instability, the mechanisms by which SR instability translates into arrhythmias and which interventions may be best suited to prevent SR instability. Although still at an initial stage of development, such interventions might represent the future of antiarrhythmic drug therapy.

Cite this article as:

Zaza Antonio and Rocchetti Marcella, Calcium Store Stability as an Antiarrhythmic Endpoint, Current Pharmaceutical Design 2015; 21 (8) . https://dx.doi.org/10.2174/1381612820666141029100650