Differential modulation of the cardiac adenosine triphosphate-sensitive potassium channel by isoflurane and halothane

Background: The cardiac adenosine triphosphate-sensitive potassium (K-ATP) channel is activated during pathophysiological episodes such as ischemia and hypoxia and may lead to beneficial effects on cardiac function. Studies of volatile anesthetic interactions with the cardiac K-ATP channel have been limited. The goal of this study was to investigate the ability of volatile anesthetics halothane and isoflurane to modulate the cardiac sarcolemmal K-ATP channel. Methods: The K-ATP channel current (I-KATP) was monitored using the whole cell configuration of the patch clamp technique from single ventricular cardiac myocytes enzymatically isolated from guinea pig hearts. I-KATP Was elicited by extracellular application of the potassium channel openers 2,4-dinitrophenol or pinacidil. Results: Volatile anesthetics modulated I-KATP in an anesthetic-dependent manner. Isoflurane facilitated the opening of the K-ATP channel. Following initial activation of 1,1 by 2,4-dinitrophenol, isoflurane at 0.5 and 1.3 mM further increased current amplitude by 40.4 +/- 11.1% and 58.4 +/- 20.6%, respectively. Similar results of isoflurane were obtained when pinacidil was used to activate I-KATP. However, isoflurane alone was unable to elicit K-ATP channel opening. In contrast, halothane inhibited I-KATP elicited by 2,4-dinitrophenol by 50.6 +/- 5.8% and 72.1 +/- 11.6% at 0.4 and 1.0 mM, respectively. When I-KATP was activated by pinacidil, halothane had no significant effect on the current. Conclusions: The cardiac sarcolemmal K-ATP channel is differentially modulated by volatile anesthetics. Isoflurane can facilitate the further opening of the K-ATP channel following initial channel activation by 2,4-dinitrophenol or pinacidil. The effect of halothane was dependent on the method of channel activation, inhibiting I-KATP activated by 2,4-dinitrophenol but not by pinacidil.