Role of Ca2+-activated Cl- channels and MLCK in slow IJP in opossum esophageal smooth muscle.
The possible contribution of Ca2+-activated Cl- channel [I(Cl(Ca))] and myosin light-chain kinase (MLCK) to nonadrenergic, noncholinergic slow inhibitory junction potentials (sIJP) was studied using conventional intracellular microelectrode recordings in circular smooth muscle of opossum esophageal body and guinea pig ileum perfused with Krebs solution containing atropine (3 microM), guanethidine (3 microM), and substance P (1 microM). In opossum esophageal circular smooth muscle, resting membrane potential (MP) was -51.9 +/- 0.7 mV (n = 89) with MP fluctuations of 1-3 mV. A single square-wave nerve stimulation of 0.5 ms duration and 80 V induced a sIJP with amplitude of 6.3 +/- 0.2 mV, half-amplitude duration of 635 +/- 19 ms, and rebound depolarization amplitude of 2.4 +/- 0.1 mV (n = 89). 9-Anthroic acid (A-9-C), niflumic acid (NFA), wortmannin, and 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9) abolished MP fluctuations, sIJP, and rebound depolarization in a concentration-dependent manner. A-9-C and NFA but not wortmannin and ML-9 hyperpolarized MP. In guinea pig ileal circular smooth muscle, nerve stimulation elicited an IJP composed of both fast (fIJP) and slow (sIJP) components, followed by rebound depolarization. NFA (200 microM) abolished sIJP and rebound depolarization but left the fIJP intact. These data suggest that in the tissues studied, activation of I(Cl(Ca)), which requires MLCK, contributes to resting MP, and that closing of I(Cl(Ca)) is responsible for sIJP.
Zhang
Yong
Y
Gastrointestinal Disease Research Unit and Departments of Medicine, Biology, and Physiology, Queen's University, Kingston, Ontario, Canada K7L 5G2.
Paterson
William G
WG
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007082:Ileum / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009544:Niflumic Acid / Q000494:pharmacology; D009893:Opossums; D019789:Tetraethylammonium / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D000873:Anthracenes; D001381:Azepines; D018118:Chloride Channels; D004791:Enzyme Inhibitors; C056218:ML 9; D009544:Niflumic Acid; D019789:Tetraethylammonium; C010030:9-anthroic acid; D009219:Myosin-Light-Chain Kinase; D002118:Calcium; D000077191:Wortmannin; D007213:Indomethacin