Volatile anaesthetic effects on Na+-Ca2+ exchange in rat cardiac myocytes.
We examined the influence of two clinically relevant concentrations (1 and 2 MAC (minimum alveolar concentration)) of halothane and sevoflurane on both efflux and reverse modes of Na+-Ca2+ exchange (NCX) in enzymatically dissociated adult rat cardiac myocytes. We hypothesised that a volatile anaesthetic-induced decrease in myocardial contractility is mediated by a reduction in intracellular calcium concentration ([Ca2+]i) via inhibition of NCX. Cells were exposed to cyclopiazonic acid and zero extracellular Na+ and Ca2+ to block sacroplasmic reticulum (SR) re-uptake and NCX efflux, respectively. As [Ca2+]i increased under these conditions, extracellular Na+ was rapidly (< 300 ms) reintroduced in the presence or absence of a volatile anaesthetic to selectively promote Ca2+ efflux via NCX. Other cells exposed to cyclopiazonic acid and ryanodine to inhibit SR Ca2+ re-uptake and release were Na+ loaded in zero extracellular Ca2+. The reintroduction of extracellular Ca2+ was used to selectively activate Ca2+ influx via NCX. Compared to controls, both 1 and 2 MAC halothane as well as sevoflurane reduced NCX-mediated efflux. The reduction in NCX-mediated influx was concentration dependent, but comparable between the two anaesthetics. Both anaesthetics at each concentration also shifted the relationship between extracellular Na+ (or extent of Na+ loading) and NCX-mediated efflux (or influx) to the right. These data indicate that despite inhibition of NCX-mediated Ca2+ efflux, volatile anaesthetics produce myocardial depression. However, the inhibition of NCX-mediated Ca2+ influx may contribute to decreased cardiac contractility. The overall effect of volatile anaesthetics on the [Ca2+]i profile is likely to be determined by the relative contributions of influx vs. efflux via NCX during each cardiac cycle.
Seckin
I
I
Department of Anaesthesiology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Sieck
G C
GC
Prakash
Y S
YS
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D018613:Microscopy, Confocal; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000077149:Sevoflurane; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D018685:Anesthetics, Inhalation; D000889:Anti-Arrhythmia Agents; D007211:Indoles; D008738:Methyl Ethers; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D000077149:Sevoflurane; D012964:Sodium; D002118:Calcium; D006221:Halothane; C000543:cyclopiazonic acid