EFFECTS OF Y-26763, A NOVEL K-CHANNEL OPENER, ON ELECTRICAL RESPONSESOF SMOOTH MUSCLES IN THE GUINEA-PIG BLADDER

Purpose: The effects of Y-26763, a novel K-channel opener, on spontane ous and carbachol-induced electrical responses of bladder smooth muscl e in guinea pig were studied. Material and Methods: Intracellular micr oelectrodes 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 b ursts of spike discharge which were sensitive to nicardipine, a Ca++-a ntagonist. Y-26763 inhibited the spike discharges with or without hype rpolarization of the membrane; the spike inhibition appeared at lower concentrations (>10(-8) M.) than the hyperpolarization (>10(-7) M.). T he effects of Y-26763 were antagonized by glibenclamide, which suggest ed 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 th e spike generation but not the depolarization induced by carbachol (10 (-6) M.) in a concentration-dependent manner. Conclusion: 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 app lications for the treatment of unstable bladders.