A Functional Link between Store-operated and TRPC Channels Revealed by the 3,5-Bis(trifluoromethyl)pyrazole Derivative, BTP2

• Published in: The Journal of biological chemistry 2005-03, Vol.280 (12), p.10997-11006
• Main Authors: He, Li-Ping, Hewavitharana, Thamara, Soboloff, Jonathan, Spassova, Maria A., Gill, Donald L.
• Format: Article
• Language: English
• Subjects: Anilides - pharmacology; Animals; Calcium - metabolism; Calcium Channels - physiology; Cation Transport Proteins - physiology; Cell Line; Chickens; Humans; Ion Channels - physiology; Rats; Thiadiazoles - pharmacology; TRPC Cation Channels; TRPV Cation Channels
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M411797200

The coupling between receptor-mediated Ca2+ store release and the activation of “store-operated” Ca2+ entry channels is an important but so far poorly understood mechanism. The transient receptor potential (TRP) superfamily of channels contains several members that may serve the function of store-operated channels (SOCs). The 3,5-bis(trifluoromethyl)pyrazole derivative, BTP2, is a recently described inhibitor of SOC activity in T-lymphocytes. We compared its action on SOC activation in a number of cell types and evaluated its modification of three specific TRP channels, canonical transient receptor potential 3 (TRPC3), TRPC5, and TRPV6, to throw light on any link between SOC and TRP channel function. Using HEK293 cells, DT40 B cells, and A7r5 smooth muscle cells, BTP2 blocked store-operated Ca2+ entry within 10 min with an IC50 of 0.1–0.3 μm. Store-operated Ca2+ entry induced by Ca2+ pump blockade or in response to muscarinic or B cell receptor activation was similarly sensitive to BTP2. Using the T3–65 clonal HEK293 cell line stably expressing TRPC3 channels, TRPC3-mediated Sr2+ entry activated by muscarinic receptors was also blocked by BTP2 with an IC50 of