Halothane, enflurane, and isoflurane stimulate calcium leakage from rabbit sarcoplasmic reticulum.
The sarcoplasmic reticulum (SR) controls uptake and release of Ca2+ in muscle. Little information is available regarding the effect of volatile anesthetics on Ca2+ release from SR isolated from normal skeletal muscle, even though an abnormality of Ca2+ handling is implicated in malignant hyperthermia. In this study we used a Ca2+ electrode to monitor continuously the release of Ca2+ from SR and the effect of volatile anesthetics on this process. We found that halothane, enflurane, and isoflurane at 0.6, 0.7, and 0.8 vol%, respectively, each increased the velocity of Ca2+ leakage by at least 150% when compared to control. Ruthenium red, a blocker of the SR Ca(2+)-release channel, was shown to have no effect on the velocity of Ca2+ leakage. Halothane and isoflurane both shortened the time at which Ca2+ leakage began (T) in a dose-dependent fashion. Halothane at 4.8 vol% decreased T from 293 +/- 21 s to 149 +/- 20 s. Isoflurane (4.8 vol%) decreased T to 203 +/- 16 s, and enflurane at 5 vol% had little effect, decreasing T to 259 +/- 19 s. We noted a marked stimulation in the ATPase activity of the SR by all three volatile anesthetics. Halothane at 0.63 vol%, isoflurane at 0.42 vol%, and enflurane at 0.62 vol% each increased ATPase activity by at least 300%. We conclude that the stimulation of the velocity of Ca2+ leakage by the volatile anesthetics is related to the more rapid depletion of ATP, but that the shortening of the onset of Ca2+ leakage is a independent phenomenon with a markedly different dose dependence.(ABSTRACT TRUNCATED AT 250 WORDS)
Blanck
T J
TJ
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.
Peterson
C V
CV
Baroody
B
B
Tegazzin
V
V
Lou
J
J
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D046508:Culture Techniques; D004737:Enflurane / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism
D004737:Enflurane; D007530:Isoflurane; D000251:Adenosine Triphosphatases; D002118:Calcium; D006221:Halothane