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

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.