Cibenzoline inhibits diazoxide- and 2,4-dinitrophenol-activated ATP-sensitive K+ channels in guinea-pig ventricular cells.
1. We have investigated the effects of diazoxide (a sulphonamide derivative) and cibenzoline (a class I antiarrhythmic drug) on ATP-sensitive K+ currents in guinea-pig ventricular cells, using whole-cell clamp techniques. 2. Diazoxide (50 microM) produced a marked shortening of action potential duration which was antagonized by 1 microM glibenclamide, an ATP-sensitive K+ channel blocker. 3. Diazoxide (50 microM) increased the quasi-steady state outward current elicited by a ramp voltage protocol (-20 mV s-1) at potentials positive to about -70 mV. This effect was completely prevented in the presence of glibenclamide (1 microM), thereby suggesting that diazoxide opens ATP-sensitive K+ channels. 4. Cibenzoline (5 microM) depressed the diazoxide-induced increases in the outward current and the pretreatment with this agent prevented the development of the diazoxide-induced outward current. 5. Cibenzoline (10 microM) reversed the 2,4-dinitrophenol (50 microM)-induced shortening of the action potential duration partially but significantly. 6. These results suggest that diazoxide activates ATP-sensitive K+ channels of guinea-pig ventricular cells and that cibenzoline, at therapeutic concentrations, inhibits this channel.
Sato
T
T
Department of Physiology, Oita Medical University, Japan.
Wu
B
B
Nakamura
S
S
Kiyosue
T
T
Arita
M
M
D019297:2,4-Dinitrophenol; D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003981:Diazoxide / Q000037:antagonists & inhibitors*; D004140:Dinitrophenols / Q000037:antagonists & inhibitors*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D004140:Dinitrophenols; D007093:Imidazoles; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D003981:Diazoxide; D019297:2,4-Dinitrophenol; D005905:Glyburide; C032151:cifenline