Inhibition of human TRPC5 channel by serum albumin

Abstract

Classical transient receptor potential (TRPC) channels are suggested to play pivotal roles in the regulation of endothelial barrier function (Gioffi and Stevens 2006, Microcirc 13, 709–23). TRPC5, like other TRPCs, is a calcium‐permeable channel that is widely expressed, including in endothelial cells (Tiruppathi et al 2006, Microcirc 13, 693–708). It is activated by a multiplicity of signals, one of which is lysophosphatidylcholine, an inflammatory factor (Flemming et al 2005, J Biol Chem 281, 4977–82; Qiao et al 2006, Am J Physiol 291 91–101). Here we show that serum albumin, which influences vascular tone and endothelial permeability (Fuentes et al 1997, J Phyiol 504, 315–26), inhibits TRPC5. Tetracycline‐inducible TRPC5‐expressing HEK 293 cells were studied using fura‐2 to measure calcium‐entry in real‐time 96‐well plate assays. Activation of TRPC5 by lysophospholipids or gadolinium was inhibited by fatty acid‐free serum albumin or recombinant human serum albumin. Boiled albumin had no effect. Electrophysiological studies showed reversible inhibition of TRPC5‐mediated current by serum albumin. The data suggest albumin may inhibit calcium entry via TRPC5 in cell types that come into contact with albumin, either constitutively or dynamically during inflammation.