Abstract
Transient receptor potential (TRP) channels mediate a wide array of sensory functions. We investigated the role of TRPC5, a poorly characterized channel widely expressed in the central and peripheral nervous system, as a potential osmosensory protein. 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-4, 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(2) levels are reduced by regulated overexpression of a lipid phosphatase. The response was restored by increasing intracellular PIP(2) levels through the patch pipette. The mechano-sensitivity of the channel was probed in the whole-cell configuration by application of steps of positive pressure through the patch pipette. Pressure-induced membrane stretch also activated TRPC5 channels, suggesting its role as a transducer of osmo-mechanical stimuli. We also demonstrated the expression of TRPC5 in sensory neurones which together with the osmo-mechanical characteristics of TRPC5 channels suggest its putative role in mechanosensory transduction events.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism
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Carbachol / pharmacology
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Cell Line
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Cell Membrane / physiology*
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Cytoplasm / drug effects
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Cytoplasm / metabolism
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Estrenes / pharmacology
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Ganglia, Spinal / metabolism
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Hippocampus / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology*
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mice
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Osmotic Pressure
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Peptides / pharmacology
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Phosphodiesterase Inhibitors / pharmacology
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / metabolism
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Pressure
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Pyrrolidinones / pharmacology
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Sensory Receptor Cells / metabolism
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Spider Venoms / pharmacology
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Stress, Mechanical
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TRPC Cation Channels / genetics
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TRPC Cation Channels / physiology*
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Thapsigargin / pharmacology
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Transfection
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Trigeminal Ganglion / metabolism
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Type C Phospholipases / antagonists & inhibitors
Substances
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Estrenes
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Intercellular Signaling Peptides and Proteins
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MTx4 protein, Grammostola spatulata
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Peptides
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Phosphodiesterase Inhibitors
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Pyrrolidinones
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Spider Venoms
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TRPC Cation Channels
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Trpc5 protein, mouse
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Thapsigargin
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Carbachol
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Phosphoric Monoester Hydrolases
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phosphoinositide 5-phosphatase
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Type C Phospholipases
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Calcium