Effects of Ibandronate Sodium, a Nitrogen-Containing Bisphosphonate, on Intermediate-Conductance Calcium-Activated Potassium Channels in Osteoclast Precursor Cells (RAW 264.7)

Sheng Nan Wu, Yan Ming Huang, Yu Kai Liao

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Ibanonate sodium (Iban), a nitrogen-containing bisphosphonate, is recognized to reduce skeletal complications through an inhibition of osteoclast-mediated bone resorption. However, how this drug interacts with ion channels in osteoclasts and creates anti-osteoclastic activity remains largely unclear. In this study, we investigated the possible effects of Iban and other related compounds on ionic currents in the osteoclast precursor RAW 264.7 cells. Iban suppressed the amplitude of whole-cell K+ currents (IK) in a concentration-dependent manner with an IC50 value of 28.9 μM. The IK amplitude was sensitive to block by TRAM-34 and Iban-mediated inhibition of IK was reversed by further addition of DCEBIO, an activator of intermediate-conductance Ca2+-activated K+ (IKCa) channels. Intracellular dialysis with Iban diminished IK amplitude and further addition of ionomycin reversed its inhibition. In 17β-estradiol-treated cells, Iban-mediated inhibition of IK remained effective. In cell-attached current recordings, Iban applied to bath did not modify single-channel conductance of IKCa channels; however, it did reduce channel activity. Iban-induced inhibition of IKCa channels was voltage-dependent. As IKCa-channel activity was suppressed by KN-93, subsequent addition of Iban did not further decrease the channel open probability. Iban could not exert any effect on inwardly rectifying K+ current in RAW 264.7 cells. Under current-clamp recordings, Iban depolarized the membrane of RAW 264.7 cells and DCEBIO reversed Iban-induced depolarization. Iban also suppressed lipopolysaccharide-stimulated migration of RAW 264.7 cells in a concentration-dependent manner. Therefore, the inhibition by Iban of IKCa channels would be an important mechanism underlying its actions on the functional activity of osteoclasts occurring in vivo.

Original languageEnglish
Pages (from-to)103-115
Number of pages13
JournalJournal of Membrane Biology
Volume248
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Physiology
  • Cell Biology

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