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High extracellular Ca2+ stimulates Ca2+-activated Cl- currents in frog parathyroid cells through the mediation of arachidonic acid cascade.

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タイトル: High extracellular Ca2+ stimulates Ca2+-activated Cl- currents in frog parathyroid cells through the mediation of arachidonic acid cascade.
著者: Okada, Yukio / Imendra, Kotapola G / Miyazaki, Toshihiro / Hotokezaka, Hitoshi / Fujiyama, Rie / Toda, Kazuo
発行日: 2011年 4月29日
出版者: Public Library of Science
引用: PLoS One, 6(4), e19158; 2011
抄録: Elevation of extracellular Ca(2+) concentration induces intracellular Ca(2+) signaling in parathyroid cells. The response is due to stimulation of the phospholipase C/Ca(2+) pathways, but the direct mechanism responsible for the rise of intracellular Ca(2+) concentration has remained elusive. Here, we describe the electrophysiological property associated with intracellular Ca(2+) signaling in frog parathyroid cells and show that Ca(2+)-activated Cl(-) channels are activated by intracellular Ca(2+) increase through an inositol 1,4,5-trisphophate (IP(3))-independent pathway. High extracellular Ca(2+) induced an outwardly-rectifying conductance in a dose-dependent manner (EC(50) ∼6 mM). The conductance was composed of an instantaneous time-independent component and a slowly activating time-dependent component and displayed a deactivating inward tail current. Extracellular Ca(2+)-induced and Ca(2+) dialysis-induced currents reversed at the equilibrium potential of Cl(-) and were inhibited by niflumic acid (a specific blocker of Ca(2+)-activated Cl(-) channel). Gramicidin-perforated whole-cell recording displayed the shift of the reversal potential in extracellular Ca(2+)-induced current, suggesting the change of intracellular Cl(-) concentration in a few minutes. Extracellular Ca(2+)-induced currents displayed a moderate dependency on guanosine triphosphate (GTP). All blockers for phospholipase C, diacylglycerol (DAG) lipase, monoacylglycerol (MAG) lipase and lipoxygenase inhibited extracellular Ca(2+)-induced current. IP(3) dialysis failed to induce conductance increase, but 2-arachidonoylglycerol (2-AG), arachidonic acid and 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HPETE) dialysis increased the conductance identical to extracellular Ca(2+)-induced conductance. These results indicate that high extracellular Ca(2+) raises intracellular Ca(2+) concentration through the DAG lipase/lipoxygenase pathway, resulting in the activation of Cl(-) conductance.
URI: http://hdl.handle.net/10069/25478
ISSN: 19326203
DOI: 10.1371/journal.pone.0019158
PubMed ID: 21559478
権利: © 2011 Okada et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:040 学術雑誌論文

引用URI : http://hdl.handle.net/10069/25478



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