EFFECTS OF POTASSIUM CHANNEL MODULATORS CROMAKALIM, TETRAETHYLAMMONIUM AND GLIBENCLAMIDE ON THE CONTRACTILITY OF THE ISOLATED HUMAN URETER

Purpose: Experiments were performed to assess the effect of the potass ium channel modulators cromakalim, tetraethylammonium (TEA) and gliben clamide on the contractility of isolated human ureteric rings. Materia ls and Methods: Segments of human distal ureter obtained from kidney d onors (leftovers) were cut into rings and suspended in an organ bath f illed with modified Tyrode solution for measurement of isometric contr actile force. The ureter was stimulated electrically or with KCl, and the contractile activity recorded on a polygraph. Results: The amplitu de of the contraction induced by electrical stimulation was not change d by glibenclamide bu was enhanced by tetraethylammonium. The resting tension of the ureter was not changed by either potassium channel inhi bitor. Cromakalim did not change the resting tension of the human uret er per se but induced a concentration-dependent inhibition of the cont ractions 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 contraction s were abolished by cromakalim whereas the tonic contractions were una ffected, Following sustained contraction induced by 25 mM, KCl, the cu mulative addition of cromakalim to the organ bath produced a concentra tion-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. Conclusi on: These results suggest that potassium channels are important in the control of human ureter contractility and that potassium channel open ers may be an alternative therapeutic indication in the treatment of h uman ureteric colic.