title: Swelling-activated Cl(-) current in isolated rabbit articular chondrocytes: inhibition by arachidonic Acid.
abstract: Articular chondrocytes play an important role in maintaining the structure and function of the cartilage in synovial joints, which is closely influenced by mechanical or osmotic stress. In the present study, isolated rabbit articular chondrocytes were examined during hyposmotic stress using the whole-cell patch-clamp method. When exposed to hyposmotic external solutions (approximately 5% or 32% decrease in osmolarity), isolated rabbit articular chondrocytes exhibited hyposmotic cell swelling, accompanied by the activation of the swelling-activated Cl(-) current (I(Cl,swell)). I(Cl,swell) was practically time-independent at potentials negative to +50 mV but exhibited rapid inactivation at more positive potentials. I(Cl,swell) was potently inhibited by the Cl(-) channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid, glibenclamide, and tamoxifen, but was little affected by pimozide. I(Cl,swell) was also found to be acutely inhibited by arachidonic acid in a concentration-dependent manner with an IC50 of 0.81 microM. The maximal effect (approximately 100% block) was obtained with 10 microM arachidonic acid. The arachidonic acid metabolites prostaglandin E(2), leukotriene B(4), and leukotriene D(4) had no appreciable effect on IC(l,swell), suggesting that the inhibitory effect of arachidonic acid did not require its metabolism. The present study thus reveals the presence of I(Cl,swell) in rabbit articular chondrocytes that exhibits high sensitivity to direct inhibition by arachidonic acid.
authors.affiliation: Department of Orthopaedic Surgery, Shiga University of Medical Science, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Isoya
authors.forename: Futoshi
authors.initials: F
authors.lastname: Toyoda
authors.forename: Shinji
authors.initials: S
authors.lastname: Imai
authors.forename: Noriaki
authors.initials: N
authors.lastname: Okumura
authors.forename: Kousuke
authors.initials: K
authors.lastname: Kumagai
authors.forename: Mariko
authors.initials: M
authors.lastname: Omatsu-Kanbe
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Kubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsusue
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology; D048429:Cell Size / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D019902:Chondrocytes / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009579:Nitrobenzoates / Q000494:pharmacology; D009997:Osmotic Pressure; D018408:Patch-Clamp Techniques; D010868:Pimozide / Q000494:pharmacology; D011817:Rabbits; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018118:Chloride Channels; D009579:Nitrobenzoates; D013629:Tamoxifen; D010868:Pimozide; D016718:Arachidonic Acid; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D005905:Glyburide