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

作者：Funabashi Kenji; Ohya Susumu; Yamamura Hisao; Hatano Noriyuki; Muraki Katsuhiko; Giles Wayne; Imaizumi Yuji^*

来源：American Journal of Physiology - Cell Physiology, 2010, 298(4): C786-C797.

DOI：10.1152/ajpcell.00469.2009

• store-operated Ca2+ entry
• nonselective cation channels
• OUMS-27
• articular cartilage

Funabashi K, Ohya S, Yamamura H, Hatano N, Muraki K, Giles W, Imaizumi Y. Accelerated Ca2+ entry by membrane hyperpolarization due to Ca2+-activated K+ channel activation in response to histamine in chondrocytes. Am J Physiol Cell Physiol 298: C786-C797, 2010. First published December 30, 2009; doi:10.1152/ajpcell.00469.2009.-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+ (K-Ca) 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+](i) rise and also membrane hyperpolarization, and both effects were mediated by the stimulation of H-1 receptors. The histamine-induced membrane hyperpolarization was attenuated to similar to 50% by large-conductance K-Ca (BK) channel blockers, and further reduced by intermediate (IK) and small conductance K-Ca (SK) channel blockers. The tonic component of histamine-induced [Ca2+](i) rise 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 K-Ca blocker cocktail also significantly reduced the store-operated Ca2+ entry (SOCE), which was iduced by Ca2+ addition after store-depletion by thapsigargin in [Ca2+](o) free solution. Our results demonstrate that the histamine-induced membrane hyperpolarization in chondrocytes due to K-Ca channel activation contributes to sustained Ca2+ entry mainly through SOCE channels in OUMS-27 cells. Thus, K-Ca channels appear to play an important role in the positive feedback mechanism of [Ca2+](i) regulation in chondrocytes in the presence of articular cartilage inflammation.

• 出版日期2010-4