Importance of Ca2+ influx by Na+/Ca2+ exchange under normal and sodium-loaded conditions in mammalian ventricles.

Na+/Ca2+ exchange (NCX) is a major Ca2+ extrusion system in cardiac myocytes, but can also mediate Ca2+ influx and trigger sarcoplasmic reticulum Ca2+ release. Under conditions such as digitalis toxicity or ischemia/reperfusion, increased [Na+]i may lead to a rise in [Ca2+]i through NCX, causing Ca2+ overload and triggered arrhythmias. Here we used an agent which selectively blocks Ca2+ influx by NCX, KB-R7943 (KBR), and assessed twitch contractions and Ca2+ transients in rat and guinea pig ventricular myocytes loaded with indo-1.