Inhibition of the human epithelial calcium channel TRPV6 by 2-aminoethoxydiphenyl borate (2-APB)

Gergely Kovacs, Nicolas Montalbetti, Alexandre Simonin, Tamas Danko, Bernadett Balazs, A. Zsembery, Matthias A. Hediger

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

TRPV6, a highly calcium-selective member of the transient receptor potential (TRP) channel superfamily, is a major pathway for calcium absorption in the fetal and adult body. It is expressed abundantly in the duodenum, the placenta and exocrine tissues. TRVP6 was postulated to contribute to store-operated calcium channel (SOC) activity in certain cell types such as exocrine cells. In this study, we tested 2-APB, a widely used SOC inhibitor on human TRPV6 (hTRPV6) activity using fluorescence imaging, patch clamp and radioactive tracer techniques in transiently and stably transfected HEK293 cells. We found that the basal calcium and cadmium influx was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells. 2-APB inhibited hTRPV6 activity in both transient and stably transfected cells. This effect was slightly sensitive toward extracellular calcium. The extracellular sodium concentration did not affect the inhibition of hTRPV6 by 2-APB. However, N-methyl- d-glucamine significantly diminished the inhibitory effect of 2-APB presumably through direct interaction with this compound. Furthermore, 2-APB inhibited the activity of TRPV6 orthologs but not human TRPV5. 2-APB may serve as a parental compound for the development of therapeutic strategies specifically targeting the hTRPV6 calcium channel.

Original languageEnglish
Pages (from-to)468-480
Number of pages13
JournalCell Calcium
Volume52
Issue number6
DOIs
Publication statusPublished - Dec 2012

Fingerprint

Calcium Channels
Calcium
HEK293 Cells
Human Activities
Radioactive Tracers
Transient Receptor Potential Channels
Optical Imaging
Cadmium
Duodenum
Placenta
2-aminoethoxydiphenyl borate
human TRPV6 protein
Sodium
Therapeutics

Keywords

  • 2-APB
  • Calcium channel
  • SOC
  • TRPV6

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Kovacs, G., Montalbetti, N., Simonin, A., Danko, T., Balazs, B., Zsembery, A., & Hediger, M. A. (2012). Inhibition of the human epithelial calcium channel TRPV6 by 2-aminoethoxydiphenyl borate (2-APB). Cell Calcium, 52(6), 468-480. https://doi.org/10.1016/j.ceca.2012.08.005

Inhibition of the human epithelial calcium channel TRPV6 by 2-aminoethoxydiphenyl borate (2-APB). / Kovacs, Gergely; Montalbetti, Nicolas; Simonin, Alexandre; Danko, Tamas; Balazs, Bernadett; Zsembery, A.; Hediger, Matthias A.

In: Cell Calcium, Vol. 52, No. 6, 12.2012, p. 468-480.

Research output: Contribution to journalArticle

Kovacs, G, Montalbetti, N, Simonin, A, Danko, T, Balazs, B, Zsembery, A & Hediger, MA 2012, 'Inhibition of the human epithelial calcium channel TRPV6 by 2-aminoethoxydiphenyl borate (2-APB)', Cell Calcium, vol. 52, no. 6, pp. 468-480. https://doi.org/10.1016/j.ceca.2012.08.005
Kovacs, Gergely ; Montalbetti, Nicolas ; Simonin, Alexandre ; Danko, Tamas ; Balazs, Bernadett ; Zsembery, A. ; Hediger, Matthias A. / Inhibition of the human epithelial calcium channel TRPV6 by 2-aminoethoxydiphenyl borate (2-APB). In: Cell Calcium. 2012 ; Vol. 52, No. 6. pp. 468-480.
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