Clinically relevant concentrations of propofol have no effect on adenosine triphosphate-sensitive potassium channels in rat ventricular myocytes.
BACKGROUND
Activation of adenosine triphosphate-sensitive potassium (K(ATP)) channels produces cardioprotective effects during ischemia. Because propofol is often used in patients who have coronary artery disease undergoing a wide variety of surgical procedures, it is important to evaluate the direct effects of propofol on K(ATP) channel activities in ventricular myocardium during ischemia.


METHODS
The effects of propofol (0.4-60.1 microg/ml) on both sarcolemmal and mitochondrial K(ATP) channel activities were investigated in single, quiescent rat ventricular myocytes. Membrane currents were recorded using cell-attached and inside-out patch clamp configurations. Flavoprotein fluorescence was measured to evaluate mitochondrial oxidation mediated by mitochondrial K(ATP) channels.


RESULTS
In the cell-attached configuration, open probability of K(ATP) channels was reduced by propofol in a concentration-dependent manner (EC(50) = 14.2 microg/ml). In the inside-out configurations, propofol inhibited K(ATP) channel activities without changing the single-channel conductance (EC(50) = 11.4 microg/ml). Propofol reduced mitochondrial oxidation in a concentration-dependent manner with an EC(50) of 14.6 microg/ml.


CONCLUSIONS
Propofol had no effect on the sarcolemmal K(ATP) channel activities in patch clamp configurations and the mitochondrial flavoprotein fluorescence induced by diazoxide at clinically relevant concentrations (< 2 microm), whereas it significantly inhibited both K(ATP) channel activities at very high, nonclinical concentrations (> 5.6 microg/ml; 31 microm).
Kawano
Takashi
T
Department of Anesthesiology, Tokushima University School of Medicine, Tokushima, Japan. bass@clin.med.tokushima-u.ac.jp
Oshita
Shuzo
S
Tsutsumi
Yasuo
Y
Tomiyama
Yoshinobu
Y
Kitahata
Hiroshi
H
Kuroda
Yasuhiro
Y
Takahashi
Akira
A
Nakaya
Yutaka
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000187:drug effects
D018686:Anesthetics, Intravenous; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D015742:Propofol