{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:21:57Z","timestamp":1774502517608,"version":"3.50.1"},"reference-count":48,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>In articular cartilage inflammation, histamine release from mast cells is a key event. It can enhance cytokine production and matrix synthesis and also promote cell proliferation by stimulating chondrocytes. In this study, the functional impact of Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>(K<jats:sub>Ca<\/jats:sub>) channels in the regulation of intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in chondrocytes in response to histamine was examined using OUMS-27 cells, as a model of chondrocytes derived from human chondrosarcoma. Application of histamine induced a significant [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>rise and also membrane hyperpolarization, and both effects were mediated by the stimulation of H<jats:sub>1<\/jats:sub>receptors. The histamine-induced membrane hyperpolarization was attenuated to \u223c50% by large-conductance K<jats:sub>Ca<\/jats:sub>(BK) channel blockers, and further reduced by intermediate (IK) and small conductance K<jats:sub>Ca<\/jats:sub>(SK) channel blockers. The tonic component of histamine-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>rise strongly depended on the presence of extracellular Ca<jats:sup>2+<\/jats:sup>([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>) and was markedly reduced by La<jats:sup>3+<\/jats:sup>or Gd<jats:sup>3+<\/jats:sup>but not by nifedipine. It was significantly attenuated by BK channel blockers, and further blocked by the cocktail of BK, IK, and SK channel blockers. The K<jats:sub>Ca<\/jats:sub>blocker cocktail also significantly reduced the store-operated Ca<jats:sup>2+<\/jats:sup>entry (SOCE), which was induced by Ca<jats:sup>2+<\/jats:sup>addition after store-depletion by thapsigargin in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>free solution. Our results demonstrate that the histamine-induced membrane hyperpolarization in chondrocytes due to K<jats:sub>Ca<\/jats:sub>channel activation contributes to sustained Ca<jats:sup>2+<\/jats:sup>entry mainly through SOCE channels in OUMS-27 cells. Thus, K<jats:sub>Ca<\/jats:sub>channels appear to play an important role in the positive feedback mechanism of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>regulation in chondrocytes in the presence of articular cartilage inflammation.<\/jats:p>","DOI":"10.1152\/ajpcell.00469.2009","type":"journal-article","created":{"date-parts":[[2009,12,31]],"date-time":"2009-12-31T03:15:54Z","timestamp":1262229354000},"page":"C786-C797","source":"Crossref","is-referenced-by-count":46,"title":["Accelerated Ca<sup>2+<\/sup>entry by membrane hyperpolarization due to Ca<sup>2+<\/sup>-activated K<sup>+<\/sup>channel activation in response to histamine in chondrocytes"],"prefix":"10.1152","volume":"298","author":[{"given":"Kenji","family":"Funabashi","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 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