Effects of potassium channel modulators cromakalim, tetraethylammonium and glibenclamide on the contractility of the isolated human ureter.

Abstract

Experiments were performed to assess the effect of the potassium channel modulators cromakalim, tetraethylammonium (TEA) and glibenclamide on the contractility of isolated human ureteric rings. Segments of human distal ureter obtained from kidney donors (leftovers) were cut into rings and suspended in an organ bath filled with modified Tyrode solution for measurement of isometric contractile force. The ureter was stimulated electrically or with KCl, and the contractile activity recorded on a polygraph. The amplitude of the contraction induced by electrical stimulation was not changed by glibenclamide but was enhanced by tetraethylammonium. The resting tension of the ureter was not changed by either potassium channel inhibitor. Cromakalim did not change the resting tension of the human ureter per se but induced a concentration-dependent inhibition of the contractions induced by electrical stimulation. This inhibitory effect of cromakalim was not changed by tetraethylammonium but was inhibited by glibenclamide. A phasic and tonic contractile response in the isolated human ureteric ring was induced by 60 mM. KCl. The phasic contractions were abolished by cromakalim whereas the tonic contractions were unaffected. Following sustained contraction induced by 25 mM. KCl, the cumulative addition of cromakalim to the organ bath produced a concentration-dependent relaxation. However, in rings precontracted with 60 mM. KCl, cromakalim at a concentration as high as 10(-5) M. did not induce relaxation. The cromakalim-induced relaxation of rings precontracted with 25 mM. KCl was significantly inhibited by glibenclamide. These results suggest that potassium channels are important in the control of human ureter contractility and that potassium channel openers may be an alternative therapeutic indication in the treatment of human ureteric colic.