Effect of K_ATP channel openers on myogenic and neurogenic responses in goat urinary bladder

Abstract

Isolated goat detrusor muscle exhibited spontaneous contractility with an irregular amplitude and frequency. The spontaneity of detrusor muscle exhibited a mean amplitude as 11.99 ± 0.83 mm and frequency as 1.37 ± 0.16/min. K_ATP-channel openers namely, cromakalim or pinacidil (10^-7-10^-4M) added cumulatively, elicited a concentration-related inhibition of both amplitude and rate of spontaneous contractions. The mean IC₅₀values for both amplitude and frequency for cromakalim were 3.3 × 10^-6<i style="">M</i> and 2.9 × 10^-6<i style="">M</i>, respectively; and for pinacidil were 2.0 × 10^-5<i style="">M</i> and 1.5 × 10^-5<i style="">M</i>, respectively. Glibenclamide, a K_ATP-channel blocker inhibited the cromakalim-induced concentration-related relaxation of spontaneous contractions with a significant increase in its mean IC₅₀. ACh -induced concentration-related contractile response was inhibited in the presence of either cromakalim (10^-4<i style="">M</i>) or pinacidil (10^-4<i style="">M</i>). The mean EC₅₀value of ACh, in the presence of cromakalim (2.5 × 10^-3<i style="">M</i>) was significantly increased as compared to the control (1.2 × 10^-6<i style="">M</i>). In the presence of glibenclamide (10^-5<i style="">M</i>) the inhibitory effect of cromakalim was significantly reduced with consequent decrease in the EC₅₀ value (1.9 × 10^-5<i style="">M</i>). Application of EFS (30 V and 5 ms) on goat urinary bladder strips at 1, 2, 5, 10, 20 and 30 Hz elicited frequency-related contractile responses. Both cromakalim and pinacidil caused a rightward shift in the frequency-related contractile response curve with significant increase in the mean EF₂₅ and EF₅₀values, respectively. In the presence of glibenclamide (10^-4<i style="">M</i>), the frequency-related inhibitory response curve was shifted to left with significant (P <0.001) increase in the mean EF₂₅,EF₅₀ and EF_75.The present results suggest that in the goat detrusor muscle, agonist and EFS-induced contractile responses were more potently inhibited by cromakalim than pinacidil with activation of glibenclamide sensitive K_ATPchannels.