Ca2+ uptake and Ca2+ release by skeletal muscle sarcoplasmic reticulum: differing sensitivity to inhalational anesthetics.
The effects of halothane, enflurane, and isoflurane were measured on two different mechanisms of Ca2+ regulation by isolated skeletal muscle sarcoplasmic reticulum (SR) membranes. A 100,000-dalton Ca2+-ATPase protein transports Ca2+ from outside to inside the SR membrane. At concentration ranges representing anesthetic levels of 0.06 to 2.3 times MAC, halothane, enflurane, and isoflurane each increased rate of Ca2+ uptake by SR. Each concentration of isoflurane produced a greater rate of Ca2+ uptake, whereas halothane and enflurane produced maximum stimulation of Ca2+ uptake at 1 and 1.6 times MAC, respectively. The second Ca2+ regulation mechanism studied was a Ca2+ release channel in the SR membrane. The release of Ca2+ via this mechanism requires a critical threshold Ca2+ load (nmol Ca2+/mg SR protein) for Ca2+-induced Ca2+ release to occur. Each anesthetic tested effectively lowered the critical Ca2+ load threshold for Ca2+ release, i.e., the Ca2+ channel was more readily induced to an open state in the presence of anesthetic. The concentrations of anesthetics having this effect on the putative Ca2+ channel were between 0.0026 and 0.078 MAC equivalents for each agent, and these concentrations are much lower than the anesthetic concentrations affecting Ca2+ uptake. These data show that in isolated skeletal muscle SR membranes a Ca2+ channel release function is altered at anesthetic concentrations far below those that change Ca2+ uptake function by a Ca2+-ATPase and below concentrations of the volatile agents producing clinical anesthesia. The Ca2+ channel effect may represent protein-anesthetic interaction, whereas the Ca2+-ATPase effect may occur by a generalized SR membrane perturbation by the anesthetics.
Nelson
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Department of Anesthesiology, University of Texas Health Science Center, Houston 77030.
Sweo
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D000776:Anesthesiology / Q000295:instrumentation; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004737:Enflurane / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D009994:Osmolar Concentration; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D004737:Enflurane; D007530:Isoflurane; D002118:Calcium; D006221:Halothane