Effects of Y-26763, A Novel K-Channel Opener, on Electrical Responses of Smooth Muscles in the Guinea Pig Bladder

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Abstract
The effects of Y-26763, a novel K-channel opener, on spontaneous and carbachol-induced electrical responses of bladder smooth muscle in guinea pig were studied.Intracellular microelectrodes were used to record membrane electrical responses from the detrusor smooth muscle of guinea pig.In most cells studied, the membranes were spontaneously active with continuous or periodic bursts of spike discharge which were sensitive to nicardipine, a Ca++ -antagonist. Y-26763 inhibited the spike discharges with or without hyperpolarization of the membrane; the spike inhibition appeared at lower concentrations (>10(-8 M.) than the hyperpolarization (>10(-7) M.). The effects of Y-26763 were antagonized by glibenclamide, which suggested an involvement of ATP-sensitive K-channels. Carbachol increased the discharge frequency of spikes, with (>10(-6)M.) or without (10(-7) M.) depolarization of the membrane. Y-26763 (>10(-7) M.) inhibited the spike generation but not the depolarization induced by carbachol (10(-6)M.) in a concentration-dependent manner.Y-26763 may directly prevent electrical excitability of bladder smooth muscles by inhibiting spike discharges and also by hyperpolarizing the membrane. The results suggest that this K-channel opener could have clinical applications for the treatment of unstable bladders.