Native TRPC7 channel activation by an inositol trisphosphate receptor-dependent mechanism

被引:33
作者
Vazquez, Guillermo
Bird, Gary St. J.
Mori, Yasuo
Putney, James W., Jr.
机构
[1] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
[2] Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Mol Biol Lab, Kyoto 6158510, Japan
关键词
D O I
10.1074/jbc.M604994200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In DT40 B lymphocytes, Canonical Transient Receptor Potential 7 (TRPC7) functions as a diacylglycerol-activated non-selective cation channel. However, previous work indicated that the non-store-operated Ca2+ entry in this cell type depends upon inositol trisphosphate receptors ( IP3R). With the cell-attached configuration oleyl-acetyl-glycerol (OAG) induced single channel activity ( 75 pS) that was not observed in TRPC7(-/-) cells but was rescued by expression of TRPC7 under conditions expected to produce relatively low levels of expression ((LowT7)TRPC7(-/-)). A DT40 cell line lacking IP3R (IP3R-/- cells) showed no OAG-induced single channel activity, but this activity was rescued by transient expression of an IP3R ((IP3R-/-)-I-IP3R). Single channel properties in (LowT7)TRPC7(-/-) or (IP3R-/-)-I-IP3R DT40 cells were indistinguishable from one another and from wildtype cells. Thus, TRPC7 forms, or is part of, the channel underlying endogenous diacylglycerol-activated currents in DT40 B lymphocytes, and this activity of native TRPC7 requires IP3R. However, with conditions expected to produce greater expression levels, TRPC7 functioned independently of the presence of IP3R. This finding may serve to resolve previously conflicting reports from expression studies of TRPC channels.
引用
收藏
页码:25250 / 25258
页数:9
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