| Title: |
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. |
| Authors: |
Peppiatt, C; Collins, T; Mackenzie, L; Conway, S; Holmes, AB; Bootman, MD; Berridge, M; Seo, J; Roderick, H |
| Publication Year: |
2016 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
The action of 2-aminoethoxydiphenyl borate (2-APB) on Ca(2+) 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 (InsP(3))-mediated Ca(2+) release and store-operated Ca(2+) entry (SOC). In addition to abrogating hormone-evoked Ca(2+) responses, 2-APB could antagonise Ca(2+) signals evoked by a membrane permeant InsP(3) ester. 2-APB also slowed the recovery of intracellular Ca(2+) signals consistent with an effect on Ca(2+) ATPases. The inhibitory action of 2-APB on InsP(3) receptors (InsP(3)Rs), SOC channels and Ca(2+) pumps persisted for several minutes after washout of the compound. Application of 2-APB to unstimulated cells had no effect on subsequent Ca(2+) 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 Ca(2+) channels or ryanodine receptors, we found that it gave a concentration-dependent long-lasting inhibition of Ca(2+) signalling in electrically-stimulated cardiac myocytes, where InsP(3)Rs 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 Ca(2+) signalling in cell types where InsP(3) and SOC are not active. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1016/S0143-4160(03)00026-3 |
| Availability: |
https://doi.org/10.1016/S0143-4160(03)00026-3; https://ora.ox.ac.uk/objects/uuid:7f073379-3b0d-47ed-8303-c785a94c00e5 |
| Rights: |
info:eu-repo/semantics/embargoedAccess |
| Accession Number: |
edsbas.4A9E8573 |
| Database: |
BASE |