Anesthetic effects on mitochondrial ATP-sensitive K channel.
BACKGROUND
Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation.


METHODS
Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured.


RESULTS
Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation.


CONCLUSIONS
Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.
Kohro
S
S
Department of Anesthesiology Research, Medical College of Wisconsin, Milwaukee 53226, USA.
Hogan
Q H
QH
Nakae
Y
Y
Yamakage
M
M
Bosnjak
Z J
ZJ
D018528:ATP-Binding Cassette Transporters; D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D005420:Flavoproteins / Q000378:metabolism; D006168:Guinea Pigs; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D054086:KATP Channels; D008738:Methyl Ethers / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010424:Pentobarbital / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying; D015742:Propofol / Q000494:pharmacology; D000077149:Sevoflurane; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D000759:Adjuvants, Anesthesia; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D003652:Decanoic Acids; D004232:Diuretics; D005420:Flavoproteins; D006880:Hydroxy Acids; D054086:KATP Channels; D008738:Methyl Ethers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D049993:Sodium Chloride Symporter Inhibitors; C092520:uK-ATP-1 potassium channel; D000077149:Sevoflurane; C052853:5-hydroxydecanoic acid; D007530:Isoflurane; D010424:Pentobarbital; D003981:Diazoxide; D015742:Propofol