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.
Pflugers Arch
; 458(6): 1049-59, 2009 Oct.
Article
em En
| MEDLINE
| ID: mdl-19543743
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 [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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Osteopetrose
/
Canais de Cloreto
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Pflugers Arch
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão