Effects of volatile anesthetics on sarcolemmal calcium transport and sarcoplasmic reticulum calcium content in isolated myocytes.
BACKGROUND
The surface membrane Ca(2+)-adenosine triphosphatase and Na(+)-Ca(2+) exchanger transport Ca(2+) out of the ventricular myocyte, competing for cytosolic Ca(2+) with the Ca(2+)-adenosine triphosphatase located in the sarcoplasmic reticulum. In this study the authors examined the effects of halothane, isoflurane, and sevoflurane on Ca(2+) extrusion from the cell and sarcoplasmic reticulum Ca(2+) 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 Ca(2+) indicator fluo-3, and electrically stimulated at 0.25 Hz to reach a steady state level of intracellular Ca(2+) stores. The effects of halothane, isoflurane, and sevoflurane (1 minimum alveolar concentration) on the peak and rate of decline of the Ca(2+) transient induced by 10 mm caffeine were examined. The peak was used as an index of sarcoplasmic reticulum Ca(2+) content, and the rate of decline was used to monitor Ca(2+) extrusion from the cell.


RESULTS
During control conditions, halothane reduced the Ca(2+) content of the sarcoplasmic reticulum, isoflurane maintained it, and sevoflurane caused it to increase. Halothane did not affect Ca(2+) extrusion from the cell, but both isoflurane and sevoflurane inhibited it. When Na(+)-Ca(2+) exchange was inhibited by ionic substitution, isoflurane and sevoflurane still reduced the rate of Ca(2+) efflux from the cell. However, when the sarcolemmal Ca(2+)-adenosine triphosphatase was inhibited by carboxyeosin, isoflurane and sevoflurane had no effect on Ca(2+) efflux.


CONCLUSIONS
These results suggest that isoflurane and sevoflurane inhibit Ca(2+) transport from the cell via the sarcolemmal Ca(2+)-adenosine triphosphatase. This effect seems to counteract the decrease in Ca(2+) influx through sarcolemmal L-type Ca(2+) channels and maintains sarcoplasmic reticulum Ca(2+) stores.
Hannon
James D
JD
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. hannon.james@mayo.edu
Cody
Mark J
MJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D005289:Ferrets; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D018685:Anesthetics, Inhalation; D002118:Calcium