Blockade of adenosine triphosphate-sensitive potassium channels by thiamylal in rat ventricular myocytes.

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Tsutsumi Y, Oshita S, Kitahata H, Kuroda Y, Kawano T, Nakaya Y

Blockade of adenosine triphosphate-sensitive potassium channels by thiamylal in rat ventricular myocytes.

Anesthesiology. 2000 Apr;92(4):1154-9.

PubMed ID

10754636 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Thiamylal	ATP-sensitive inward rectifier potassium channel 11	Protein	Humans	Yes	Inhibitor	Details
Thiamylal	ATP-sensitive inward rectifier potassium channel 8	Protein	Humans	Yes	Inhibitor	Details