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

Abstract

Background: The cardiac adenosine triphosphate-sensitive potassium (KATP) 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 KATP 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 KATP channel. Methods: The KATP channel current (IKATP) was monitored using the whole cell configuration of the patch clamp technique from single ventricular cardiac myocytes enzymatically isolated from guinea pig hearts. IKATP was elicited by extracellular application of the potassium channel openers 2,4-dinitrophenol or pinacidil. Results: Volatile anesthetics modulated IKATP in an anesthetic-dependent manner. Isoflurane facilitated the opening of the KATP channel. Following initial activation of IKATP 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 IKATP. However, isoflurane alone was unable to elicit KATP channel opening. In contrast, halothane inhibited IKATP elicited by 2,4-dinitrophenol by 50.6 ± 5.8% and 72.1 ±- 11.6% at 0.4 and 1.0 mM, respectively. When IKATP was activated by pinacidil, halothane had no significant effect on the current. Conclusions: The cardiac sarcolemmal KATP channel is differentially modulated by volatile anesthetics. Isoflurane can facilitate the further opening of the KATP channel following initial channel activation by 2,4-dinitrophenol or pinacidil. The effect of halothane was dependent on the method of channel activation, inhibiting IKATP activated by 2,4-dinitrophenol but not by pinacidil.