2-Aminoethoxydiphenyl borate (2-APB) antagonises inositol 1,4,5-trisphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channels

Claire M. Peppiatt, Tony J. Collins, Lauren Mackenzie, Stuart J. Conway, Andrew B. Holmes, Martin D. Bootman, Michael J. Berridge, Jeong T. Seo, H. Llewelyn Roderick

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232 Citations (Scopus)

Abstract

The action of 2-aminoethoxydiphenyl borate (2-APB) on Ca2+ signalling in HeLa cells and cardiac myocytes was investigated. Consistent with other studies, we found that superfusion of cells with 2-APB rapidly inhibited inositol 1,4,5-trisphosphate (InsP3 -mediated Ca2+ release and store-operated Ca2+ entry (SOC). In addition to abrogating hormone-evoked Ca2+ responses, 2-APB could antagonise Ca2+ signals evoked by a membrane permeant InsP3 ester. 2-APB also slowed the recovery of intracellular Ca2+ signals consistent with an effect on Ca2+ ATPases. The inhibitory action of 2-APB on InsP3 receptors (InsP3Rs), SOC channels and Ca2+ pumps persisted for several minutes after washout of the compound. Application of 2-APB to unstimulated cells had no effect on subsequent Ca2+ responses suggesting that it has a use-dependent action. Mitochondria in cells treated with 2-APB showed a rapid and slowly reversible swelling. 2-APB did not cause the mitochondria to depolarise, but it reduced the extent of mitochondrial calcium uptake. Although 2-APB has been demonstrated not to affect voltage-operated Ca2+ channels or ryanodine receptors, we found that it gave a concentration-dependent long-lasting inhibition of Ca2+ signalling in electrically-stimulated cardiac myocytes, where InsP3Rs and SOC channels do not play a significant role. Our data suggest that 2-APB has multiple cellular targets, a use-dependent action, is difficult to reverse and may affect Ca2+ signalling in cell types where InsP3 and SOC are not active.

Original languageEnglish
Pages (from-to)97-108
Number of pages12
JournalCell Calcium
Volume34
Issue number1
DOIs
Publication statusPublished - 2003 Jul 1

Bibliographical note

Funding Information:
The authors would like to thank Dr. Jyrki Kukkonen (University of Uppsala) for many interesting exchanges on the subject of 2-APB. This work was funded by the BBSRC. CMP was supported BBSRC studentship. MDB is a Royal Society University Research Fellow.

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

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