Volatile anaesthetic effects on Na+-Ca2+ exchange in rat cardiac myocytes

1. We examined the influence of two clinically relevant concentrations (1 a nd 2 MAC (minimum alveolar concentration)) of halothane and sevoflurane on both efflux and reverse modes of Na+-Ca2+ exchange (NCX) in enzymatically d issociated adult rat cardiac myocytes. We hypothesised that a volatile anae sthetic-induced decrease in myocardial contractility is mediated by a reduc tion in intracellular calcium concentration ([Ca2+](i)) via inhibition of N CS. 2. Cells were exposed to cyclopiazonic acid and zero extracellular Na+ and Ca2+ to l,lock sacroplasmic reticulum (SR) re-uptake and NCX efflux, respec tively. As [Ca2+](i) increased under these conditions, extracellular Na+ wa s rapidly (< 300 ms) reintroduced in the presence ol absence of a volatile anaesthetic to selectively promote Ca2+ efflux via NCS. Other cells exposed to cyclopiazonic acid and ryanodine to inhibit SR Ca2+ re-uptake and relea se were Na+ loaded in zero extracellular Ca2+. The reintroduction of extrac ellular Ca2+ was used to selectively activate Ca2+ influx via. NCX. 3. Compared to controls, both 1 and 2 MAC halothane as well as sevoflurane reduced NCX-mediated efflux. The reduction in NCX-mediated influx was conce ntration dependent, but comparable between the two anaesthetics. Both anaes thetics at each concentration also shifted the relationship between extrace llular Na+ (or extent of Nac loading) and NCX-mediated efflux (or influx) t o the right. 4. These data indicate that despite inhibition of NCX-mecliated Ca2+ efflux , volatile anaesthetics produce myocardial depression. However, the inhibit ion of NCX-mediated Ca2+ influx may contribute to decreased cardiac contrac tility. The overall effect of volatile anaesthetics on the [Ca2+](i) profil e is likely to he determined by the relative contributions of influx vs. ef flux via NCX during each cardiac cycle.