Isoflurane-induced facilitation of the cardiac sarcolemmal K(ATP) channel.
BACKGROUND
Volatile anesthetics have cardioprotective effects that mimic ischemic preconditioning, including the involvement of adenosine triphosphate-sensitive potassium (K(ATP)) channels. However, evidence for a direct effect of volatile anesthetic on the K(ATP) channel is limited. In this study, the effects of isoflurane on the cardiac sarcolemmal K(ATP) channel were investigated.


METHODS
Single ventricular myocytes were enzymatically isolated from guinea pig hearts. Whole cell and single-channel configurations, specifically the cell-attached and inside-out patch mode, of the patch clamp technique were used to monitor sarcolemmal K(ATP) channel current.


RESULTS
In the cell-attached patch configuration, 2,4-dinitrophenol (150 microm) opened the sarcolemmal K(ATP) channel. Isoflurane (0.5 mm) further increased channel open probability and the number of active channels in the patch. In contrast, in the inside-out patch experiments, isoflurane had no significant effect on the K(ATP) channel activated by low ATP (0.2-0.5 mm). In addition, isoflurane had no effect on the K(ATP) channel when activated by adenosine diphosphate, adenosine + guanosine triphosphate, bimakalim, and 2,4-dinitrophenol under inside-out patch configurations. When K(ATP) current was monitored in the whole cell mode, isoflurane alone was unable to elicit channel opening. However, during sustained protein kinase C activation by 12,13-dibutyrate, isoflurane activated the K(ATP) current that was sensitive to glibenclamide. In contrast, isoflurane had no effect on the K(ATP) channel activated by 12,13-dibutyrate in a cell-free environment.


CONCLUSIONS
Isoflurane facilitated the opening of the sarcolemmal K(ATP) channel in the intact cell, but not in an excised, inside-out patch. The isoflurane effect was not due to a direct interaction with the K(ATP) channel protein, but required an intracellular component, likely including the translocation of specific protein kinase C isoforms. This suggests that the sarcolemmal K(ATP) channel may have a significant role in anesthetic-induced preconditioning.
Department of Anesthesiology, Medical College Wisconsin, Milwaukee, Wisconsin 53226, USA.
Kazuhiro
K
Fujimoto
Zeljko J
ZJ
Bosnjak
Wai-Meng
WM
Kwok
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011493:Protein Kinase C / Q000502:physiology
D018685:Anesthetics, Inhalation; D001578:Benzopyrans; D004095:Dihydropyridines; D015221:Potassium Channels; C061050:bimakalim; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007530:Isoflurane; D011493:Protein Kinase C; D000241:Adenosine; D019297:2,4-Dinitrophenol