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 I(KATP) 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.
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. wmkwok@mcw.edu
Wai-Meng
WM
Kwok
Anne T
AT
Martinelli
Kazuhiro
K
Fujimoto
Akihiro
A
Suzuki
Anna
A
Stadnicka
Zeljko J
ZJ
Bosnjak
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D015221:Potassium Channels; D020110:Pinacidil; D000255:Adenosine Triphosphate; D007530:Isoflurane; D019297:2,4-Dinitrophenol; D006221:Halothane