Blockade of adenosine triphosphate-sensitive potassium channels by thiamylal in rat ventricular myocytes.
BACKGROUND
The adenosine triphosphate (ATP)-sensitive potassium (KATP) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of thiamylal on the activities of KATP channels in isolated rat ventricular myocytes during simulated ischemia.


METHODS
Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, KATP channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l thiamylal. The open probability was determined from current-amplitude histograms. In the inside-out configuration, the current-voltage relation was obtained before and after the application of thiamylal (50 mg/1).


RESULTS
In the cell-attached configuration, 2,4-dinitrophenol caused frequent channel opening. 2,4-Dinitrophenol-induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were KATP channels. Open probability of KATP channels was reduced by thiamylal in a concentration-dependent manner. KATP channels could be activated in the inside-out configuration because of the absence of ATP. Thiamylal inhibited KATP channel activity without changing the single-channel conductance.


CONCLUSIONS
The results obtained in this study indicate that thiamylal inhibits KATP channel activities in cell-attached and inside-out patches, suggesting a direct action of this drug on these channels.
Tsutsumi
Y
Y
Department of Anesthesiology, Tokushima University School of Medicine, Japan. tsutsumi@clin.med.tokushima-u.ac.jp
Oshita
S
S
Kitahata
H
H
Kuroda
Y
Y
Kawano
T
T
Nakaya
Y
Y
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D018528:ATP-Binding Cassette Transporters; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002469:Cell Separation; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000009:adverse effects*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D013840:Thiamylal / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D018686:Anesthetics, Intravenous; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D014475:Uncoupling Agents; C092520:uK-ATP-1 potassium channel; D013840:Thiamylal; D019297:2,4-Dinitrophenol; D005905:Glyburide