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Vol. 296, Issue 3, 669-675, March 2001

Functional Implication of Spare ATP-Sensitive K+ Channels in Bladder Smooth Muscle Cells

Char-Chang Shieh, Jianlin Feng, Steven A. Buckner, Jorge D. Brioni, Michael J. Coghlan, James P. Sullivan and Murali Gopalakrishnan

Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois

ATP-sensitive K+ (KATP) channels play important roles in the regulation of excitability in urinary bladder smooth muscle cells. Patch-clamp studies revealed that the current density was about 9-fold higher in the pig bladder smooth muscle cells, compared with guinea pig, although the rank order of potencies for suppression of electrical field-stimulated contraction of bladder strips by KATP channel openers (KCOs) showed a nearly 1:1 correlation between pig and guinea pig. To investigate the existence of spare KATP channels, P1075-evoked current and membrane potential responses were studied in bladder smooth muscle cells. During a 10-min exposure to P1075 (10 µM), KATP currents ran down by ~30.5%, whereas membrane hyperpolarization remained constant. P1075 evoked membrane hyperpolarization with an EC50 value of 0.20 ± 0.02 µM, comparable to that required for smooth muscle relaxation (EC50 = 0.11 ± 0.01 µM). However, these potencies are 6-fold higher than those required for current activation (EC50 = 0.73 ± 0.4 µM). These findings demonstrate that the reduction in membrane excitability by KCOs is associated with membrane hyperpolarization, and that a low amount of KATP channel opening is sufficient to suppress bladder smooth muscle contraction.

0022-3565/01/2963-0669$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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