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OBJECTIVE The effect of a potassium channel opener, YM934, on the contractile response to excitatory neurotransmitters was investigated in isolated pig detrusor smooth muscle. METHODS Electrical field stimulation (EFS; 5 second trains, 50 V, 0.8 msec. duration), alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) or carbachol (3 x 10(-8) to 10(-6) M.) produced a contractile response in isolated pig detrusor smooth muscle. The effect of YM934 on the contractile responses was evaluated in comparison with the antagonism of the putative cotransmitters, acetylcholine and ATP. RESULTS A tetrodotoxin-sensitive, frequency-dependent contractile response to electrical field stimulation was obtained. Atropine (3 x 10(-8) M.) significantly inhibited the contractile response at high frequencies, whereas alpha, beta-MeATP (5 x 10(-6) M.) (desensitizer of P2X-purinoceptors) significantly inhibited the response at low frequencies. YM934 (10(-8) to 10(-7) M.) dose-dependently inhibited the nerve-mediated contractile responses to all frequencies but preferentially at low frequencies, by analogy with alpha, beta-MeATP. A combination of YM934 (3 x 10(-8) M.) and atropine (3 x 10(-8) M.) reduced the response at all frequencies to between 10 and 20% of control, an effect similar to that obtained with alpha, beta-MeATP (5 x 10(-6) M.) and atropine (3 x 10(-8) M.). In addition, YM934 (3 x 10(-8) M.) markedly inhibited the contractile response induced by exogenously applied alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) but only slightly inhibited the contractile response induced by exogenously applied carbachol (3 x 10(-8) to 10(-6) M.). CONCLUSIONS These results suggest that YM934 may hyperpolarize the membrane of pig detrusor smooth muscle through the opening of ATP-sensitive potassium channels and, as a result, may functionally inhibit the contractile response to purinergic nerve stimulation that elicits the membrane depolarization.
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