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

Okada, Yukio

Imendra, Kotapola G

Miyazaki, Toshihiro

Hotokezaka, Hitoshi

Fujiyama, Rie

Toda, Kazuo

    • © 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.
  • 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.
  • identifier:PLoS One, 6(4), e19158; 2011
PublisherPublic Library of Science
Date Issued 2011-04-29
NIItypejournal article
Identifier URI
  • isIdenticalTo PMID 21559478
  • isIdenticalTo DOI
    • ISSN 1932-6203
    • PLoS One
    6(4), e19158