2-aminoethoxydiphenyl borane activates a novel calcium-permeable cation channel.
The membrane-permeable, noncompetitive inositol 1,4,5-trisphosphate (IP3)-receptor inhibitor 2-aminoethoxydiphenyl borane (2-APB) has been widely used to probe for IP3-receptor involvement in calcium signaling pathways. However, a number of recent studies in different cell types revealed other sites of action of 2-APB. In this study, we examined the influence of 2-APB on capacitative calcium entry and intracellular Ca2+ concentrations in rat basophilic leukemia (RBL-2H3 m1) cells. 2-APB was found to inhibit capacitative calcium entry, but at concentrations greater than 50 microM, a new effect of 2-APB was observed. When capacitative calcium entry was blocked with Gd3+, 2-APB caused an increase in cytoplasmic Ca2+. This increase in intracellular Ca2+ was not caused by altered buffering of cytoplasmic Ca2+ and was not caused by or in any way affected by the depletion of intracellular Ca2+ stores. Associated with the increase in intracellular Ca2+, in the presence of 2 mM Ca2+, 2-APB activated single channels in the plasma membrane with a conductance of approximately 50 pS. These channels seem to be nonselective cation channels; monovalent cations are the major carriers of current, but finite permeability to Ca2+ leads to a significant intracellular Ca2+ signal. Experiments with excised patches indicate that 2-APB activates these channels from the outer aspect of the cell membrane. This effect of 2-APB further illustrates the complex actions of this compound and reveals the presence in RBL-2H3 m1 cells of a novel, ligand-gated calcium-permeable channel.
Braun
Franz-Josef
FJ
National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA.
Aziz
Omar
O
Putney
James W
JW
D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D004594:Electrophysiology; D007473:Ion Channels / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001896:Boron Compounds; D015220:Calcium Channels; D002412:Cations; D007473:Ion Channels; D012964:Sodium; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium