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Here we show that hypoosmotic stimulation activates TRPC5 channels resulting in a large calcium influx. The response to osmotically induced membrane stretch is blocked by GsMTx\u20104, an inhibitor of stretch activated ion channels. Direct hypoosmotic activation of TRPC5 is independent of phospholipase C function. However, the osmotic response is inhibited in a cell line in which PIP<jats:sub>2<\/jats:sub> levels are reduced by regulated overexpression of a lipid phosphatase. The response was restored by increasing intracellular PIP<jats:sub>2<\/jats:sub> levels through the patch pipette. The mechano\u2010sensitivity of the channel was probed in the whole\u2010cell configuration by application of steps of positive pressure through the patch pipette. Pressure\u2010induced membrane stretch also activated TRPC5 channels, suggesting its role as a transducer of osmo\u2010mechanical stimuli. We also demonstrated the expression of TRPC5 in sensory neurones which together with the osmo\u2010mechanical characteristics of TRPC5 channels suggest its putative role in mechanosensory transduction events.<\/jats:p>","DOI":"10.1113\/jphysiol.2008.161257","type":"journal-article","created":{"date-parts":[[2008,10,3]],"date-time":"2008-10-03T00:14:07Z","timestamp":1222992847000},"page":"5633-5649","source":"Crossref","is-referenced-by-count":136,"title":["Hypoosmotic\u2010 and pressure\u2010induced membrane stretch activate TRPC5 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