Abstract
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. KBR (5 μM) did not alter control steady-state twitch contractions or Ca2+ transients at 0.5 Hz in rat, but significantly decreased them in guinea pig myocytes. When cells were Na+-loaded by perfusion of strophanthidin (50 μM), the addition of KBR reduced diastolic [Ca2+]i and abolished spontaneous Ca2+ oscillations. In guinea pig papillary muscles exposed to substrate-free hypoxic medium for 60 min, KBR (10 μM applied 10 min before and during reoxygenation) reduced both the incidence and duration of reoxygenation-induced arrhythmias. KBR also enhanced the recovery of developed tension after reoxygenation. It is concluded that (1) the importance of Ca2+ influx via NCX for normal excitation-contraction coupling is species-dependent, and (2) Ca2+ influx via NCX may be critical in causing myocardial Ca2+ overload and triggered activities induced by cardiac glycoside or reoxygenation.
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Satoh, H., Mukai, M., Urushida, T. et al. Importance of Ca2+ influx by Na+/Ca2+ exchange under normal and sodium-loaded conditions in mammalian ventricles. Mol Cell Biochem 242, 11–17 (2003). https://doi.org/10.1023/A:1021192318882
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DOI: https://doi.org/10.1023/A:1021192318882