AJP - Cell Physiology, Vol 264, Issue 5 C1190-C1200, Copyright © 1993 by American Physiological Society

ARTICLES

ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder

A. D. Bonev and M. T. Nelson
Department of Pharmacology, University of Vermont, Colchester 05446-2500.

We explored the possibility that ATP-sensitive potassium (KATP) channels exist in urinary bladder smooth muscle, since synthetic openers (e.g., lemakalim) of KATP channels in other tissues relax bladder smooth muscle. Unitary currents through single potassium channels and whole cell potassium currents were measured in smooth muscle cells isolated from the detrusor muscle of the guinea pig bladder. Lemakalim (10 microM) increased whole cell K+ currents by 50 pA at -80 mV with 60 mM external K+ when the cells were dialyzed with 0.1 mM ATP and 140 mM K+. Glibenclamide (10 microM), a sulfonylurea blocker of KATP channels in other tissues, inhibited the entire lemakalim-stimulated current as well as 19 pA of the steady-state K+ current. Glibenclamide-sensitive K+ currents were not dependent on voltage. Increasing intracellular ATP from 0.1 to 3.0 mM reduced the glibenclamide-sensitive K+ current in both the presence and absence of lemakalim by about fourfold. External barium (100 microM) which blocks KATP channels in skeletal muscle reduced KATP channel currents in bladder smooth muscle by 50% at -80 mV. Lemakalim (10 microM) increased the open-state probability of single K+ channels in outside-out patches (with 0.1 mM internal ATP) by sixfold. The single-channel conductance was approximately 7 pS at 0 mV with a physiological K+ gradient. This single-channel conductance was in accord with estimates of conductance made from noise analysis of the lemakalim-induced whole cell current. Glibenclamide inhibited these channels. The number of channels per cell was estimated to be approximately 425. We conclude that urinary bladder smooth muscle has KATP channels and that these channels can be opened by the K+ channel opening drug, lemakalim, and blocked by external glibenclamide and barium. We propose that modulation of these channels may regulate bladder contractility.

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