Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin-Darby canine kidney cells

Wu, Sheng-Nan, Chen, Hui-Zhen, Chou, Yu-Hung, Huang, Yan-Ming and Lo, Yi-Ching (2015) Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin-Darby canine kidney cells. Toxicology Reports, 2 1182-1193. doi:10.1016/j.toxrep.2015.08.010


Author Wu, Sheng-Nan
Chen, Hui-Zhen
Chou, Yu-Hung
Huang, Yan-Ming
Lo, Yi-Ching
Title Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin-Darby canine kidney cells
Journal name Toxicology Reports   Check publisher's open access policy
ISSN 2214-7500
Publication date 2015-08-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.toxrep.2015.08.010
Open Access Status DOI
Volume 2
Start page 1182
End page 1193
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Formatted abstract
The nitrogen-containing bisphosphonates used for management of the patients with osteoporosis were reported to influence the function of renal tubular cells. However, how nitrogen-containing bisphosphates exert any effects on ion currents remains controversial. The effects of ibandronate (Iban), a nitrogen-containing bisphosphonate, on ionic channels, including two types of Ca2+-activated K+ (KCa) channels, namely, large-conductance KCa (BKCa) and intermediate-conductance KCa (IKCa) channels, were investigated in Madin–Darby canine kidney (MDCK) cells. In whole-cell current recordings, Iban suppressed the amplitude of voltage-gated K+ current elicited by long ramp pulse. Addition of Iban caused a reduction of BKCa channels accompanied by a right shift in the activation curve of BKCa channels, despite no change in single-channel conductance. Ca2+ sensitivity of these channels was modified in the presence of this compound; however, the magnitude of Iban-mediated decrease in BKCa-channel activity under membrane stretch with different negative pressure remained unchanged. Iban suppressed the probability of BKCa-channel openings linked primarily to a shortening in the slow component of mean open time in these channels. The dissociation constant needed for Iban-mediated suppression of mean open time in MDCK cells was 12.2 μM. Additionally, cell exposure to Iban suppressed the activity of IKCa channels, and DC-EBIO or 9-phenanthrol effectively reversed its suppression. Under current-clamp configuration, Iban depolarized the cells and DC-EBIO or PF573228 reversed its depolarizing effect. Taken together, the inhibitory action of Iban on KCa-channel activity may contribute to the underlying mechanism of pharmacological or toxicological actions of Iban and its structurally similar bisphosphonates on renal tubular cells occurring in vivo.
Keyword Ibandronate
MDCK cell
Large-conductance Ca2+-activated K+ channel
Intermediate-conductance Ca2+-activated K+ channel
Membrane potential
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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