Accelerated Ca2+entry by membrane hyperpolarization due to Ca2+-activated K+channel activation in response to histamine in chondrocytes

Autor: Kenji Funabashi, Susumu Ohya, Noriyuki Hatano, Yuji Imaizumi, Katsuhiko Muraki, Hisao Yamamura, Wayne R. Giles
Rok vydání: 2010
Předmět:
Zdroj: American Journal of Physiology-Cell Physiology. 298:C786-C797
ISSN: 1522-1563
0363-6143
Popis: 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 Ca2+-activated K+(KCa) channels in the regulation of intracellular Ca2+concentration ([Ca2+]i) 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 [Ca2+]irise and also membrane hyperpolarization, and both effects were mediated by the stimulation of H1receptors. The histamine-induced membrane hyperpolarization was attenuated to ∼50% by large-conductance KCa(BK) channel blockers, and further reduced by intermediate (IK) and small conductance KCa(SK) channel blockers. The tonic component of histamine-induced [Ca2+]irise strongly depended on the presence of extracellular Ca2+([Ca2+]o) and was markedly reduced by La3+or Gd3+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 KCablocker cocktail also significantly reduced the store-operated Ca2+entry (SOCE), which was induced by Ca2+addition after store-depletion by thapsigargin in [Ca2+]ofree solution. Our results demonstrate that the histamine-induced membrane hyperpolarization in chondrocytes due to KCachannel activation contributes to sustained Ca2+entry mainly through SOCE channels in OUMS-27 cells. Thus, KCachannels appear to play an important role in the positive feedback mechanism of [Ca2+]iregulation in chondrocytes in the presence of articular cartilage inflammation.
Databáze: OpenAIRE