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.
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 [Ca(2+)]( 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.
Kajiya
Hiroshi
H
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Tamura 2-15-1, Sawara-ku, Fukuoka, 8140193, Japan. kajiya@college.fdcnet.ac.jp
Okamoto
Fujio
F
Ohgi
Kimiko
K
Nakao
Akihiro
A
Fukushima
Hidefumi
H
Okabe
Koji
K
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D002460:Cell Line; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism*; D010022:Osteopetrosis / Q000235:genetics / Q000378:metabolism*
C097540:CLCN7 protein, human; D018118:Chloride Channels