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Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry.
J Biol Chem. 2008 Jul 11; 283(28):19265-73.JB

Abstract

Store-operated Ca2+ entry (SOCE) is likely the most common mode of regulated influx of Ca2+ into cells. However, only a limited number of pharmacological agents have been shown to modulate this process. 2-Aminoethyldiphenyl borate (2-APB) is a widely used experimental tool that activates and then inhibits SOCE and the underlying calcium release-activated Ca2+ current (I CRAC). The mechanism by which depleted stores activates SOCE involves complex cellular movements of an endoplasmic reticulum Ca2+ sensor, STIM1, which redistributes to puncta near the plasma membrane and, in some manner, activates plasma membrane channels comprising Orai1, -2, and -3 subunits. We show here that 2-APB blocks puncta formation of fluorescently tagged STIM1 in HEK293 cells. Accordingly, 2-APB also inhibited SOCE and I(CRAC)-like currents in cells co-expressing STIM1 with the CRAC channel subunit, Orai1, with similar potency. However, 2-APB inhibited STIM1 puncta formation less well in cells co-expressing Orai1, indicating that the inhibitory effects of 2-APB are not solely dependent upon STIM1 reversal. Further, 2-APB only partially inhibited SOCE and current in cells co-expressing STIM1 and Orai2 and activated sustained currents in HEK293 cells expressing Orai3 and STIM1. Interestingly, the Orai3-dependent currents activated by 2-APB showed large outward currents at potentials greater than +50 mV. Finally, Orai3, and to a lesser extent Orai1, could be directly activated by 2-APB, independently of internal Ca2+ stores and STIM1. These data reveal novel and complex actions of 2-APB effects on SOCE that can be attributed to effects on both STIM1 as well as Orai channel subunits.

Authors+Show Affiliations

Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

18487204

Citation

DeHaven, Wayne I., et al. "Complex Actions of 2-aminoethyldiphenyl Borate On Store-operated Calcium Entry." The Journal of Biological Chemistry, vol. 283, no. 28, 2008, pp. 19265-73.
DeHaven WI, Smyth JT, Boyles RR, et al. Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry. J Biol Chem. 2008;283(28):19265-73.
DeHaven, W. I., Smyth, J. T., Boyles, R. R., Bird, G. S., & Putney, J. W. (2008). Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry. The Journal of Biological Chemistry, 283(28), 19265-73. https://doi.org/10.1074/jbc.M801535200
DeHaven WI, et al. Complex Actions of 2-aminoethyldiphenyl Borate On Store-operated Calcium Entry. J Biol Chem. 2008 Jul 11;283(28):19265-73. PubMed PMID: 18487204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry. AU - DeHaven,Wayne I, AU - Smyth,Jeremy T, AU - Boyles,Rebecca R, AU - Bird,Gary S, AU - Putney,James W,Jr Y1 - 2008/05/16/ PY - 2008/5/20/pubmed PY - 2008/8/30/medline PY - 2008/5/20/entrez SP - 19265 EP - 73 JF - The Journal of biological chemistry JO - J Biol Chem VL - 283 IS - 28 N2 - Store-operated Ca2+ entry (SOCE) is likely the most common mode of regulated influx of Ca2+ into cells. However, only a limited number of pharmacological agents have been shown to modulate this process. 2-Aminoethyldiphenyl borate (2-APB) is a widely used experimental tool that activates and then inhibits SOCE and the underlying calcium release-activated Ca2+ current (I CRAC). The mechanism by which depleted stores activates SOCE involves complex cellular movements of an endoplasmic reticulum Ca2+ sensor, STIM1, which redistributes to puncta near the plasma membrane and, in some manner, activates plasma membrane channels comprising Orai1, -2, and -3 subunits. We show here that 2-APB blocks puncta formation of fluorescently tagged STIM1 in HEK293 cells. Accordingly, 2-APB also inhibited SOCE and I(CRAC)-like currents in cells co-expressing STIM1 with the CRAC channel subunit, Orai1, with similar potency. However, 2-APB inhibited STIM1 puncta formation less well in cells co-expressing Orai1, indicating that the inhibitory effects of 2-APB are not solely dependent upon STIM1 reversal. Further, 2-APB only partially inhibited SOCE and current in cells co-expressing STIM1 and Orai2 and activated sustained currents in HEK293 cells expressing Orai3 and STIM1. Interestingly, the Orai3-dependent currents activated by 2-APB showed large outward currents at potentials greater than +50 mV. Finally, Orai3, and to a lesser extent Orai1, could be directly activated by 2-APB, independently of internal Ca2+ stores and STIM1. These data reveal novel and complex actions of 2-APB effects on SOCE that can be attributed to effects on both STIM1 as well as Orai channel subunits. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/18487204/Complex_actions_of_2_aminoethyldiphenyl_borate_on_store_operated_calcium_entry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)81380-5 DB - PRIME DP - Unbound Medicine ER -