Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid
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 whol...
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| Format: | Article |
| Language: | English |
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Elsevier
2009-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131931285X |
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| author | Eiji Isoya Futoshi Toyoda Shinji Imai Noriaki Okumura Kousuke Kumagai Mariko Omatsu-Kanbe Mitsuhiko Kubo Hiroshi Matsuura Yoshitaka Matsusue |
| author_facet | Eiji Isoya Futoshi Toyoda Shinji Imai Noriaki Okumura Kousuke Kumagai Mariko Omatsu-Kanbe Mitsuhiko Kubo Hiroshi Matsuura Yoshitaka Matsusue |
| author_sort | Eiji Isoya |
| collection | DOAJ |
| description | 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 (ICl,swell). ICl,swell was practically time-independent at potentials negative to +50 mV but exhibited rapid inactivation at more positive potentials. ICl,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. ICl,swell was also found to be acutely inhibited by arachidonic acid in a concentration-dependent manner with an IC50 of 0.81 μM. The maximal effect (approximately 100% block) was obtained with 10 μM arachidonic acid. The arachidonic acid metabolites prostaglandin E2, leukotriene B4, and leukotriene D4 had no appreciable effect on ICl,swell, suggesting that the inhibitory effect of arachidonic acid did not require its metabolism. The present study thus reveals the presence of ICl,swell in rabbit articular chondrocytes that exhibits high sensitivity to direct inhibition by arachidonic acid. Keywords:: chondrocyte, swelling-activated Cl− current, arachidonic acid, 5-nitro-2-(3-phenylpropylamino)benzoic acid, pimozide |
| first_indexed | 2024-12-20T12:23:19Z |
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| id | doaj.art-c6dd638c69c148e5a6a757d84bf07761 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-20T12:23:19Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-c6dd638c69c148e5a6a757d84bf077612022-12-21T19:40:56ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-011092293304Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic AcidEiji Isoya0Futoshi Toyoda1Shinji Imai2Noriaki Okumura3Kousuke Kumagai4Mariko Omatsu-Kanbe5Mitsuhiko Kubo6Hiroshi Matsuura7Yoshitaka Matsusue8Department of Orthopaedic Surgery, Otsu, Shiga 520-2192, Japan; Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Orthopaedic Surgery, Otsu, Shiga 520-2192, JapanDepartment of Orthopaedic Surgery, Otsu, Shiga 520-2192, Japan; Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Orthopaedic Surgery, Otsu, Shiga 520-2192, Japan; Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Orthopaedic Surgery, Otsu, Shiga 520-2192, JapanDepartment of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; Corresponding author. matuurah@belle.shiga-med.ac.jpDepartment of Orthopaedic Surgery, Otsu, Shiga 520-2192, JapanArticular 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 (ICl,swell). ICl,swell was practically time-independent at potentials negative to +50 mV but exhibited rapid inactivation at more positive potentials. ICl,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. ICl,swell was also found to be acutely inhibited by arachidonic acid in a concentration-dependent manner with an IC50 of 0.81 μM. The maximal effect (approximately 100% block) was obtained with 10 μM arachidonic acid. The arachidonic acid metabolites prostaglandin E2, leukotriene B4, and leukotriene D4 had no appreciable effect on ICl,swell, suggesting that the inhibitory effect of arachidonic acid did not require its metabolism. The present study thus reveals the presence of ICl,swell in rabbit articular chondrocytes that exhibits high sensitivity to direct inhibition by arachidonic acid. Keywords:: chondrocyte, swelling-activated Cl− current, arachidonic acid, 5-nitro-2-(3-phenylpropylamino)benzoic acid, pimozidehttp://www.sciencedirect.com/science/article/pii/S134786131931285X |
| spellingShingle | Eiji Isoya Futoshi Toyoda Shinji Imai Noriaki Okumura Kousuke Kumagai Mariko Omatsu-Kanbe Mitsuhiko Kubo Hiroshi Matsuura Yoshitaka Matsusue Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid Journal of Pharmacological Sciences |
| title | Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid |
| title_full | Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid |
| title_fullStr | Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid |
| title_full_unstemmed | Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid |
| title_short | Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid |
| title_sort | swelling activated cl current in isolated rabbit articular chondrocytes inhibition by arachidonic acid |
| url | http://www.sciencedirect.com/science/article/pii/S134786131931285X |
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