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

Cell Calcium. 2003 Jul;34(1):97-108. doi: 10.1016/s0143-4160(03)00026-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron Compounds / pharmacology*
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Calcium Signaling / drug effects*
  • Calcium Signaling / physiology
  • Calcium-Transporting ATPases / antagonists & inhibitors*
  • Calcium-Transporting ATPases / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • HeLa Cells
  • Humans
  • Inositol 1,4,5-Trisphosphate / antagonists & inhibitors*
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Inositol 1,4,5-Trisphosphate Receptors
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Myocytes, Cardiac
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / metabolism


  • Boron Compounds
  • Calcium Channels
  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Inositol 1,4,5-Trisphosphate
  • 2-aminoethoxydiphenyl borate
  • Calcium-Transporting ATPases