title: Mechanism of active repolarization of inhibitory junction potential in murine colon.
abstract: Enteric inhibitory responses in gastrointestinal (GI) smooth muscles involve membrane hyperpolarization that transiently reduce the excitability of GI muscles. We examined the possibility that an active repolarization mechanism participates in the restoration of resting membrane potential after fast inhibitory junction potentials (IJPs) in the murine colon. Previously, we showed these cells express a voltage-dependent nonselective cation conductance (NSCC) that might participate in active repolarization of IJPs. Colonic smooth muscle cells were impaled with micro-electrodes and voltage responses to nerve-evoked IJPs, and locally applied ATP were recorded. Ba2+ (500 muM), a blocker of the NSCC, slowed the rate of repolarization of IJPs. We also tested the effects of Ba2+, Ni2+, and mibefradil, all blockers of the NSCC, on responses to locally applied ATP. Spritzes of ATP caused transient hyperpolarization, and the durations of these responses were significantly increased by the blockers of the NSCC. We considered whether NSCC blockers might affect ATP metabolism and found that Ni2+ decreased ATP breakdown in colonic muscles. Mibefradil had no effect on ATP metabolism. Because both Ni2+ and mibefradil had similar effects on prolonging responses to ATP, it appears that restoration of resting membrane potential after ATP spritzes is not primarily due to ATP metabolism. Neurally released enteric inhibitory transmitter and locally applied ATP resulted in transient hyperpolarizations of murine colonic muscles. Recovery of membrane potential after these responses appears to involve an active repolarization mechanism due to activation of the voltage-dependent NSCC expressed by these cells.
authors.affiliation: Dept. of Physiology and Cell Biology, Univ. of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Salah A
authors.initials: SA
authors.lastname: Baker
authors.forename: Violeta
authors.initials: V
authors.lastname: Mutafova-Yambolieva
authors.forename: Kevin
authors.initials: K
authors.lastname: Monaghan
authors.forename: Burton
authors.initials: B
authors.lastname: Horowitz
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Sang Don
authors.initials: SD
authors.lastname: Koh
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008564:Membrane Potentials / Q000502:physiology; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002412:Cations; D007473:Ion Channels; D001464:Barium; D020748:Mibefradil; D009532:Nickel; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases