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. 1993 Feb;108(2):549–556. doi: 10.1111/j.1476-5381.1993.tb12839.x

Cibenzoline inhibits diazoxide- and 2,4-dinitrophenol-activated ATP-sensitive K+ channels in guinea-pig ventricular cells.

T Sato 1, B Wu 1, S Nakamura 1, T Kiyosue 1, M Arita 1
PMCID: PMC1908002  PMID: 8448602

Abstract

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.

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Selected References

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