Calcium transport by cardiac sarcoplasmic reticulum: modulation of halothane action by substrate concentration and pH.
The response of calcium transport to halothane by the cardiac sarcoplasmic reticulum (SR) was investigated to determine whether the SR is a site for anesthetic depression of the myocardium. It was observed that halothane could both stimulate (by 800%) and inhibit (by 500%) calcium transport. The varied effects are dependent on adenosine triphosphate (ATP) and calcium and hydrogen ion concentrations. At 2.25% halothane, the Km for ATP is decreased from 2.35 to 0.712 mM and Vmax is decreased from 292 to 149 nmoles/mg/2min. It was found that the steady-state level of calcium in the SR was decreased by 33% by halothane at pH 6.9, whereas halothane had no effect at pH 7.3. It was concluded that the SR is an unlikely site of halothane-induced myocardial depression in the normal heart when substrate concentrations and pH are maintained. In the ischemic heart in which the pH and substrate concentration have decreased, the interaction of halothane with the SR might contribute to a decrease in Ca2+ for contraction.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*
D000255:Adenosine Triphosphate; D002118:Calcium; D006221:Halothane