Effects of volatile anesthetics on sarcolemmal calcium transport and sarcoplasmic reticulum calcium content in isolated myocytes

Background: The surface membrane Ca2+-adenosilie triphosphatase and Na+-Ca2+ exchanger transport Ca2+ out of the ventricular myocyte, competing for cytosolic Ca2+ with the Ca2+-adenosine triphosphatase located in the sarcoplasmic reticulum. In this study the authors examined the effects of halothane, isoflurane, and sevoflurane on Ca2+ extrusion from the cell and sarcoplasmic reticulum Ca2+ content. Methods: Single myocytes from the right ventricular free wall of adult male ferret hearts were isolated, loaded with the acetoxymethyl. ester of the fluorescent Ca2+ indicator fluo-3, and electrically stimulated at 0.25 Hz to reach a steady state level of intracellular Ca2+ stores. The effects of halothane, isoflurane, and sevoflurane (I minimum alveolar concentration) oil the peak and rate of decline of the Ca2+ transient induced by 10 mM caffeine were examined. The peak was used as ail index of sarcoplasmic reticulum Ca2+ content, and the rate of decline was used to monitor Ca2+ extrusion from the cell. Results: During control conditions, halothane reduced the Ca2+ content of the sarcoplasmic reticulum, isoflurane maintained it, and sevoflurane caused it to increase. Halothane did not affect Ca2+ extrusion from the cell, but both isoflurane and sevoflurane inhibited it. When Na+-Ca2+ exchange was inhibited by ionic substitution, isoflurane and sevoflurane still reduced the rate of Ca2+ efflux from the cell. However, when the sarcolemmal Ca2+-adenosine triphosphatase was inhibited by carboxycosin, isoflurane and sevoflurane had no effect on Ca2+ efflux. Conclusions: These results suggest that isoflurane and sevoflurane inhibit Ca2+ transport from the cell via the sarcolemmal Ca2+-adenosine triphosphatase. This effect seems to counteract the decrease in Ca2+ influx through sarcolemmal L-type Ca2+ channels, and maintains sarcoplasmic reticulum Ca2+ Stores.