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Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1

  • Cell and Molecular Physiology
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Abstract

Among the classical transient receptor potential (TRPC) subfamily, TRPC1 is described as a mechanosensitive and store-operated channel proposed to be activated by hypoosmotic cell swelling and positive pipette pressure as well as regulated by the filling status of intracellular Ca2+ stores. However, evidence for a physiological role of TRPC1 may most compellingly be obtained by the analysis of a TRPC1-deficient mouse model. Therefore, we have developed and analyzed TRPC1−/− mice. Pressure-induced constriction of cerebral arteries was not impaired in TRPC1−/− mice. Smooth muscle cells from cerebral arteries activated by hypoosmotic swelling and positive pipette pressure showed no significant differences in cation currents compared to wild-type cells. Moreover, smooth muscle cells of TRPC1−/− mice isolated from thoracic aortas and cerebral arteries showed no change in store-operated cation influx induced by thapsigargin, inositol-1,4,5 trisphosphate, and cyclopiazonic acid compared to cells from wild-type mice. In contrast to these results, small interference RNAs decreasing the expression of stromal interaction molecule 1 (STIM1) inhibited thapsigargin-induced store-operated cation influx, demonstrating that STIM1 and TRPC1 are mutually independent. These findings also imply that, as opposed to current concepts, TRPC1 is not an obligatory component of store-operated and stretch-activated ion channel complexes in vascular smooth muscle cells.

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Acknowledgments

We thank Eva Braun, Winfried Lorenz, and Susanne Ziegler for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (MG, AD, and TG) and by a grant from the National Heart, Lung and Blood Institute, US Department of Health and Human Services to LB.

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Correspondence to Alexander Dietrich.

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Dietrich, A., Kalwa, H., Storch, U. et al. Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1. Pflugers Arch - Eur J Physiol 455, 465–477 (2007). https://doi.org/10.1007/s00424-007-0314-3

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  • DOI: https://doi.org/10.1007/s00424-007-0314-3

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