RRC ID 51622
著者 Kuno M, Li G, Moriura Y, Hino Y, Kawawaki J, Sakai H.
タイトル Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells.
ジャーナル Pflugers Arch
Abstract Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H(+)-ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient across the plasma membrane could generate a force driving protons into the cells. Proton influx mechanisms during the acid exposure are largely unknown, however. In this study, we investigated extracellular-acid-inducible proton influx currents in osteoclast-like cells derived from a macrophage cell line (RAW264). Decreasing extracellular pH to <5.5 induced non-ohmic inward currents. The reversal potentials depended on the pH gradients across the membrane and were independent of concentrations of Na(+), Cl(-), and HCO3 (-), suggesting that they were carried largely by protons. The acid-inducible proton influx currents were not inhibited by amiloride, a widely used blocker for cation channels/transporters, or by 4,4'-diisothiocyanato-2,2'-stilbenesulfonate(DIDS) which blocks anion channels/transporters. Additionally, the currents were not significantly affected by V-ATPase inhibitors, bafilomycin A1 and N,N'-dicyclohexylcarbodiimide. Extracellular Ca(2+) (10 mM) did not affect the currents, but 1 mM ZnCl2 decreased the currents partially. The intracellular pH in the vicinity of the plasma membrane was dropped by the acid-inducible H(+) influx currents, which caused overshoot of the voltage-gated H(+) channels after removal of acids. The H(+) influx currents were smaller in undifferentiated, mononuclear RAW cells and were negligible in COS7 cells. These data suggest that the acid-inducible H(+) influx (H(+) leak) pathway may be an additional mechanism modifying the pH environments of osteoclasts upon exposure to strong acids.
巻・号 468(5)
ページ 837-47
公開日 2016-5-1
DOI 10.1007/s00424-016-1796-7
PII 10.1007/s00424-016-1796-7
PMID 26843093
MeSH 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology Action Potentials* Animals COS Cells Calcium / pharmacology Cell Membrane / drug effects Cell Membrane / metabolism Chlorides / pharmacology Chlorocebus aethiops Hydrogen-Ion Concentration Ion Channels / drug effects Ion Channels / metabolism* Mice Osteoclasts / metabolism* Protons* Zinc Compounds / pharmacology
IF 3.158
引用数 5
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)