Hashitani H, Suzuki H, Kumazawa J
Department of Physiology, Nagoya City University Medical School, Nagoya, Japan.
J Urol. 1996 Apr;155(4):1454-8.
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.
研究新型钾通道开放剂Y - 26763对豚鼠膀胱平滑肌自发和卡巴胆碱诱导的电反应的影响。
采用细胞内微电极记录豚鼠逼尿肌平滑肌的膜电反应。
在大多数研究的细胞中，膜具有自发活性，伴有连续或周期性的动作电位发放，这些发放对钙离子拮抗剂硝苯地平敏感。Y - 26763无论是否使膜超极化均能抑制动作电位发放；动作电位抑制在较低浓度（>10(-8)M）时出现，而超极化在较高浓度（>10(-7)M）时出现。Y - 26763的作用被格列本脲拮抗，提示ATP敏感性钾通道参与其中。卡巴胆碱增加动作电位发放频率，在膜去极化（>10(-6)M）或未去极化（10(-7)M）时均如此。Y - 26763（>10(-7)M）以浓度依赖方式抑制卡巴胆碱（10(-6)M）诱导的动作电位产生，但不抑制其诱导的去极化。
Y - 26763可能通过抑制动作电位发放以及使膜超极化直接阻止膀胱平滑肌的电兴奋性。结果提示这种钾通道开放剂可能在不稳定膀胱的治疗中有临床应用价值。
