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- W6742453 abstract "Transient receptor potential channels (TRPC6) is shown to mediate Ca2+ entry independent of ER store depletion by DAG, and is therefore called receptor operated channels (ROC). TRPC1 mediates Ca2+ entry in response to endoplasmic reticulum (ER) store depletion by IP3, and represents the store operated calcium channels (SOC). The prevailing view is that TRPC6 and TRPC1 function in an independent manner. We tested the hypothesis that TRPC6 and TRPC1 interact to regulate the rise in intracellular Ca2+ and thereby increase pulmonary microvessel permeability. Pulmonary endothelial cells isolated from TRPC6 or TRPC1 null mice failed to increase cytosolic Ca2+ in response to thrombin. We show that both TRPC6 and TRPC1 null mice do not develop pulmonary edema in response to thrombin which activates both ROC and SOC. Next, we used thapsigargin or DAG analog OAG which directly activates SOC or ROC to delineate the intricacies between TRPC6 and TRPC1 regulation of Ca2+ entry. We show that thapsigargin attenuated Ca2+ entry that rapidly decayed in TRPC1 null cells, whereas it did not significantly increase Ca2+ entry in TRPC6 lacking cells. Consistently we show that thapsigargin failed to induce detectable increase in microvessel permeability in TRPC1 or TRPC6 null mice lungs. Loss of TRPC6 prevented OAG induced Ca2+ entry and lung microvessel permeability. Deletion of TRPC1 had modest effect on OAG induced Ca2+ entry as well as pulmonary microvessel permeability. Our data indicate that TRPC6 and TRPC1 co-ordinate to mediate SOC dependent Ca2+ entry in endothelial cells to signal increased lung microvessel permeability." @default.
- W6742453 created "2016-06-24" @default.
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- W6742453 date "2010-04-01" @default.
- W6742453 modified "2023-10-16" @default.
- W6742453 title "TRPC6 and TRPC1 functionally interact to mediate Ca2+ entry in endothelial cells to induce lung vascular permeability" @default.
- W6742453 doi "https://doi.org/10.1096/fasebj.24.1_supplement.598.16" @default.
- W6742453 hasPublicationYear "2010" @default.
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