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Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect.
- Source :
-
British Journal of Pharmacology . Jun2005, Vol. 145 Issue 4, p405-414. 10p. - Publication Year :
- 2005
-
Abstract
- 1 2-aminoethoxydiphenyl borate (2-APB) has been widely used to examine the roles of inositol 1,4,5-trisphosphate receptors (IP3Rs) and store-operated Ca2+ entry and is an emerging modulator of cationic channels encoded by transient receptor potential (TRP) genes. 2 Using Ca2+-indicator dye and patch-clamp recording we first examined the blocking effect of 2-APB on human TRPC5 channels expressed in HEK-293 cells. 3 The concentration-response curve has an IC50 of 20 microM and slope close to 1.0, suggesting one 2-APB molecule binds per channel. The blocking effect is not shared by other Ca2+ channel blockers including methoxyverapamil, nifedipine, N-propargylnitrendipine, or berberine. 4 In whole-cell and excised membrane patch recordings, 2-APB acts from the extracellular but not intracellular face of the membrane. 5 Block of TRPC5 by 2-APB is less at positive voltages, suggesting that it enters the electric field or acts by modulating channel gating. 6 2-APB also blocks TRPC6 and TRPM3 expressed in HEK-293 cells, but not TRPM2. 7 Block of TRP channels by 2-APB may be relevant to cell proliferation because 2-APB has a greater inhibitory effect on proliferation in cells overexpressing TRPC5. 8 Our data indicate a specific and functionally important binding site on TRPC5 that enables block by 2-APB. The site is only available via an extracellular route and the block shows mild voltage-dependence. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CALCIUM antagonists
*ALKALOIDS
*ANIMAL experimentation
*BIOLOGICAL transport
*BORON compounds
*CALCIUM
*CARRIER proteins
*CELL lines
*COMPARATIVE studies
*CYTOLOGICAL techniques
*DOSE-effect relationship in pharmacology
*ELECTRIC stimulation
*GENETIC techniques
*RESEARCH methodology
*MEDICAL cooperation
*MICE
*NIFEDIPINE
*RESEARCH
*TIME
*VERAPAMIL
*EVALUATION research
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 145
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 119422476
- Full Text :
- https://doi.org/10.1038/sj.bjp.0706197