title: Calcium store stability as an antiarrhythmic endpoint.
abstract: Cardiac arrhythmias are electrical phenomena; thus, sarcolemmal ion channels have long been considered as targets of antiarrhythmic therapy. The contribution of abnormal intracellular Ca(2+) handling to digitalis-induced arrhythmogenesis is an old concept; however, the role of abnormal Ca(2+) 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 Ca(2+) store (sarcoplasmic reticulum, SR) is crucial to physiological Ca(2+) handling; when it is compromised, Ca(2+) may be released independently from excitation and lead to secondary perturbation of membrane potential. Ca(2+) store stability depends on the interplay between sarcolemmal and SR "effectors" (ion channels and transports), which are mutually linked by Ca(2+)-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.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zaza
authors.affiliation: Universita degli Studi Milano- Bicocca, Dipartimento di Biotecnologie & Bioscienze, P.za della Scienza 2, 20126 Milano (IT). antonio.zaza@unimib.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rocchetti
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D002118:Calcium