Purpose: 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.
Materials and methods: Intracellular microelectrodes were used to record membrane electrical responses from the detrusor smooth muscle of guinea pig.
Results: 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.
Conclusions: 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.