Interaction of imipramine and K⁺ channel blockers on detrusor muscle strips isolated from canine urinary bladder

The study was undertaken to examine the possibility of the involvement of K⁺ channels in the mechanism of relaxant-action of imipramine on the isolated canine detrusor muscle strips. Canine urinary bladder were isolated, and smooth muscle strips of 15 mm long and 2 mm wide from the mid-portion of anterior wall were made in the Tyrode solution of 0 ~ 4°C. The strips were prepared for isometric myography in Biancani's isolated muscle chamber containing 1 ml of Tyrode solution, which was maintained with pH 7.4 by aeration with 95% O₂/5%CO₂ at 37°C. RP 52891, a non-specific K⁺ channel opener, concentration-dependently suppressed the spontaneous phasic contractions of the detruser strips. Imipramine, a tricyclic antidepressant, also reduced the spontaneous contractions in a concentration-dependent manner. RP 52891 was more potent than imipramine (p < 0.05), and imipramine was more efficient than RP 52891 (p < 0.05). Procaine, a voltage-dependent K⁺ channel blocker, glibenclamide, an ATP-dependent K⁺ channel blocker, and apamin, a calcium-dependent K⁺ channel blocker antagonized the relaxant effect of RP 52891, but not of imipramine. Imipramine reduced the electric field stimulation (EFS)-induced contractions concentration-dependently. None of the K⁺ channel blockers employed for this study, procaine, glibenclamide or apamin antagonized the inhibitory action of imipramine on the EFS-induced contraction. These results suggest that in canine detrusor, the K⁺ channels of the characteristics of voltage-dependent, ATP-dependent and/or calcium-dependent are exist, and the inhibitory action of imipramine on the contractility of the detrusor is independent from the K⁺ channels.