Carvedilol and its non b-blocking analog VK-II-86 prevent digitalis-induced Ca2+ waves in cardiac myocyte

Abstract

Cardiotonic glycosides inhibit the sarcolemmal Na+/ K+-ATPase and cause an increase in intracellular Na+, which reduces Ca++ extrusion through the Na+/Ca++ exchanger. The result is an increase in sarcoplasmic reticulum (SR) Ca++ load and cardiac contractility. However, these compounds have associated arrhythmic effects due to the occurrence of spontaneous SR Ca++ waves as a result of SR Ca++ overload and CaMKII-dependent phosphorylation of RyR2...