title: 2-aminoethyl diphenyl borinate (2-APB) inhibits TRPM7 channels through an intracellular acidification mechanism.
abstract: 2-APB is a widely used compound in ion channel research. It affects numerous channels including inositol 1,4,5-trisphosphate receptors, store-operated calcium channels and TRP channels, TRPV3 and TRPM7 among them. A characteristic property of TRPM7 channels is their sensitivity to intracellular Mg ( 2+) and pH. Using patch clamp electrophysiology we find that in Jurkat T lymphocytes, 100-300 µM extracellular 2-APB reversibly inhibits TRPM7 channels when internal HEPES concentration is low (1 mM). Increasing the concentration to 140 mM abolishes the 2-APB effect. Using single-cell fluorescence pH video imaging, we show that at concentrations of 100 µM and higher, 2-APB potently acidifies the cytoplasm. We conclude that TRPM7 sensitivity to 2-APB is not direct but rather, can be explained by cytoplasmic acidification and a resulting channel inhibition.
authors.affiliation: Department of Neuroscience, Wright State University, Dayton, OH, USA.
authors.forename: Rikki
authors.initials: R
authors.lastname: Chokshi
authors.forename: Petronilla
authors.initials: P
authors.lastname: Fruasaha
authors.forename: J Ashot
authors.initials: JA
authors.lastname: Kozak
mesh_terms: D001896:Boron Compounds / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects; D019169:Jurkat Cells; D008274:Magnesium / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001896:Boron Compounds; D050053:TRPM Cation Channels; C109986:2-aminoethoxydiphenyl borate; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D008274:Magnesium