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.
Original language | English |
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Pages (from-to) | 1049-1059 |
Number of pages | 11 |
Journal | Pflugers Archiv European Journal of Physiology |
Volume | 458 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2009 |
Externally published | Yes |
Keywords
- Autosomal dominant osteopetrosis type II
- Bone resorption
- Chloride channel-7
- Osteoclasts
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Physiology (medical)