title: Volume-activated chloride currents in interstitial cells of Cajal.
abstract: Interstitial cells of Cajal (ICC) undergo marked morphological changes on contraction of the musculature, making it essential to understand properties of mechanosensitive ion channels. The whole cell patch-clamp technique was used to identify and to characterize volume-activated Cl- currents in ICC cultured through the explant technique. Hypotonic solutions (approximately 210 mosM) activated an outwardly rectifying current, which reversed near the equilibrium potential for Cl-. Time-dependent inactivation occurred only at pulse potentials of +80 mV, with a time constant of 478 +/- 182 ms. The degree of outward rectification was calculated using a rectification index, the ratio between the slope conductances of +65 and -55 mV, which was 13.9 +/- 1.5 at 76 mM initial extracellular Cl- concentration. The sequence of relative anion permeability of the outwardly rectifying Cl- channel was I- > Cl- > aspartate-. The chloride channel blockers, DIDS and 5-nitro-2-(3-phenlypropl-amino)benzoic acid, caused a voltage-dependent block of the outwardly rectifying Cl- current, inhibition occurring primarily at depolarized potentials. On exposure to hypotonic solution, the slope conductance significantly increased at the resting membrane potential (-70 mV) from 1.2 +/- 0.2 to 2.0 +/- 0.4 nS and at the slow-wave plateau potential (-35 mV) from 2.1 +/- 0.3 to 5.0 +/- 1.0 nS. The current was constitutively active in ICC and contributed to the resting membrane potential and excitability at the slow-wave plateau. In conclusion, swelling or volume change will depolarize ICC through activation of outwardly rectifying chloride channels, thereby increasing cell excitability.
authors.affiliation: McMaster University, Intestinal Disease Programme, Department of Medicine, Hamilton, Ontario, Canada.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Mckay
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jan D
authors.initials: JD
authors.lastname: Huizinga
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D048430:Cell Shape; D048429:Cell Size; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004553:Electric Conductivity; D007421:Intestine, Small / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid