Would modulation of intracellular Ca2+ be antiarrhythmic?
Under several types of conditions, reversal of steps of excitation-contraction coupling (RECC) can give rise to nondriven electrical activity. In this review we explore those conditions for several cardiac cell types (SA, atrial, Purkinje, ventricular cells). We find that abnormal spontaneous Ca2+ release from intracellular Ca2+ stores, aberrant Ca2+ influx from sarcolemmal channels or abnormal Ca2+ surges in nonuniform muscle can be the initiators of the RECC. Often, with such increases in Ca2+, spontaneous Ca2+ waves occur and lead to membrane depolarizations. Because the change in membrane voltage is produced by Ca2+-dependent changes in ion channel function, we also review here what is known about the molecular interaction of Ca2+ and several Ca2+-dependent processes, including the intracellular Ca2+ release channels implicated in the genetic basis of some forms of human arrhythmias. Finally, we review what is known about the effectiveness of several agents in modifying such Ca2+-dependent arrhythmias.
Boyden
Penelope A
PA
Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, NY 10032, USA. pab4@columbia.edu
ter Keurs
Henk
H
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D002118:Calcium