Pflügers Archiv - European Journal of Physiology

, 458:1049

Characteristics of ClC7 Cl channels and their inhibition in mutant (G215R) associated with autosomal dominant osteopetrosis type II in native osteoclasts and hClcn7 gene-expressing cells

  • Hiroshi Kajiya
  • Fujio Okamoto
  • Kimiko Ohgi
  • Akihiro Nakao
  • Hidefumi Fukushima
  • Koji Okabe
Ion Channels, Receptors and Transporters

DOI: 10.1007/s00424-009-0689-4

Cite this article as:
Kajiya, H., Okamoto, F., Ohgi, K. et al. Pflugers Arch - Eur J Physiol (2009) 458: 1049. doi:10.1007/s00424-009-0689-4

Abstract

ClC7 Cl channels (Clcn7) are crucial for osteoclastic bone resorption and have heterozygous mutation in autosomal osteopetrosis type II (ADO II) patients. Although extracellular acidification is known to induce ClC7 Cl currents in Clcn7-transfected oocytes, other characteristics of this acid-induced Cl current, as well as the effects of mutant Clcn7 in ADO II, remain to be determined. The present study showed that extracellular acidification evoked outward Cl currents in mouse osteoclasts. Expression of wild-type human Clcn7 in HEK293 cells also induced a significant increase in acid-activated Cl currents. These acid-activated Cl currents were independent of intracellular acidification and [Ca2+]i increase. HEK293 cells with the Clcn7 mutation associated with ADO II at G215R did not display these Cl currents. These results suggest that osteoclastic ClC7 Cl channels are activated under extracellar acidification and suppressed in Clcn7 mutant associated with ADO II during bone resorption.

Keywords

Chloride channel-7OsteoclastsAutosomal dominant osteopetrosis type IIBone resorption

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Hiroshi Kajiya
    • 1
  • Fujio Okamoto
    • 1
  • Kimiko Ohgi
    • 1
  • Akihiro Nakao
    • 1
  • Hidefumi Fukushima
    • 1
  • Koji Okabe
    • 1
  1. 1.Department of Physiological Science and Molecular BiologyFukuoka Dental CollegeFukuokaJapan