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

Sheng-Nan Wu, Hui Zhen Chen, Yu Hung Chou, Yan Ming Huang, Yi Ching Lo

研究成果: Article

3 引文 (Scopus)

摘要

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 12.2μM. 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.

原文English
頁(從 - 到)1182-1193
頁數12
期刊Toxicology Reports
2
DOIs
出版狀態Published - 2015 八月 1

指紋

Calcium-Activated Potassium Channels
Madin Darby Canine Kidney Cells
Diphosphonates
Nitrogen
ibandronic acid
Kidney
Architectural Accessibility
Clamping devices
Patch-Clamp Techniques
Ion Channels
Toxicology
Osteoporosis
Chemical activation
Pharmacology
Ions
Membranes

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

引用此文

@article{00565fe186e747439956105cacbac8e6,
title = "Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin-Darby canine kidney cells",
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 12.2μM. 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.",
author = "Sheng-Nan Wu and Chen, {Hui Zhen} and Chou, {Yu Hung} and Huang, {Yan Ming} and Lo, {Yi Ching}",
year = "2015",
month = "8",
day = "1",
doi = "10.1016/j.toxrep.2015.08.010",
language = "English",
volume = "2",
pages = "1182--1193",
journal = "Toxicology Reports",
issn = "2214-7500",
publisher = "Elsevier Scientific Publishers Ireland",

}

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; Lo, Yi Ching.

於: Toxicology Reports, 卷 2, 01.08.2015, p. 1182-1193.

研究成果: Article

TY - JOUR

T1 - Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin-Darby canine kidney cells

AU - Wu, Sheng-Nan

AU - Chen, Hui Zhen

AU - Chou, Yu Hung

AU - Huang, Yan Ming

AU - Lo, Yi Ching

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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 12.2μM. 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.

AB - 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 12.2μM. 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.

UR - http://www.scopus.com/inward/record.url?scp=84940533564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940533564&partnerID=8YFLogxK

U2 - 10.1016/j.toxrep.2015.08.010

DO - 10.1016/j.toxrep.2015.08.010

M3 - Article

AN - SCOPUS:84940533564

VL - 2

SP - 1182

EP - 1193

JO - Toxicology Reports

JF - Toxicology Reports

SN - 2214-7500

ER -