Functional implication of spare ATP-sensitive K(+) channels in bladder smooth muscle cells.
ATP-sensitive K(+) (K(ATP)) 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 K(ATP) channel openers (KCOs) showed a nearly 1:1 correlation between pig and guinea pig. To investigate the existence of spare K(ATP) channels, P1075-evoked current and membrane potential responses were studied in bladder smooth muscle cells. During a 10-min exposure to P1075 (10 microM), K(ATP) currents ran down by approximately 30.5%, whereas membrane hyperpolarization remained constant. P1075 evoked membrane hyperpolarization with an EC(50) value of 0.20 +/- 0.02 microM, comparable to that required for smooth muscle relaxation (EC(50) = 0.11 +/- 0.01 microM). However, these potencies are 6-fold higher than those required for current activation (EC(50) = 0.73 +/- 0.4 microM). These findings demonstrate that the reduction in membrane excitability by KCOs is associated with membrane hyperpolarization, and that a low amount of K(ATP) channel opening is sufficient to suppress bladder smooth muscle contraction.
Shieh
C C
CC
Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-6125, USA.
Feng
J
J
Buckner
S A
SA
Brioni
J D
JD
Coghlan
M J
MJ
Sullivan
J P
JP
Gopalakrishnan
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D004347:Drug Interactions; D004594:Electrophysiology; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000819:agonists / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels; D011725:Pyridines / Q000494:pharmacology; D013552:Swine; D001743:Urinary Bladder / Q000166:cytology / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000577:Amides; D001577:Benzophenones; D006146:Guanidines; D008565:Membrane Proteins; D015221:Potassium Channels; D011725:Pyridines; D014665:Vasodilator Agents; C095007:Zeneca ZD 6169; C117780:mitochondrial K(ATP) channel; C073896:N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine; D020110:Pinacidil; D000109:Acetylcholine