G protein-coupled receptor signalling potentiates the osmo-mechanical activation of TRPC5 channels
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Title: | G protein-coupled receptor signalling potentiates the osmo-mechanical activation of TRPC5 channels |
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Authors: | Jemal, Imane | Soriano, Sergi | Conte, Anna Lucia | Morenilla, Cruz | Gomis, Ana |
Research Group/s: | Fisiología de Membranas |
Center, Department or Service: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Keywords: | TRP channels | G protein-coupled receptors | Osmo-mechanical activation | H1 receptor |
Knowledge Area: | Fisiología |
Issue Date: | Nov-2013 |
Publisher: | Springer Berlin Heidelberg |
Citation: | Pflügers Archiv - European Journal of Physiology. 2013, Nov. doi:10.1007/s00424-013-1392-z |
Abstract: | TRPC5 is an ion channel permeable to monovalent and divalent cations that is widely expressed in different tissues. Although implicated in the control of neurite extension and in the growth cone morphology of hippocampal neurons, as well as in fear-related behaviour, the mechanisms by which TRPC5 is activated remain poorly understood. TRPC5 is known to be activated downstream of Gq-coupled receptors and by membrane stretch, and since there is evidence that mechanical stress may directly activate Gq-coupled receptors, we examined the relationship between the activation of TRPC5 by the type 1 histamine receptor and osmotic stress. Using calcium imaging and patch clamp recordings, we found that a higher proportion of cells expressing TRPC5 respond to hypoosmotic solution when they co-express H1R. This response is associated with a phospholipase C-dependent increase in the cells internal calcium concentration, which is abolished on depletion of calcium stores. We also found that the hypoosmotic stimulus that provokes mechanical stress drives the translocation of TRPC5 to the plasma membrane by a mechanism dependent on PI3K. This increase in TRPC5 at the plasma membrane augments the proportion of cells that respond to hypoosmotic stimulation. Together, these results suggest that hypoosmotic cell-swelling activates Gq-coupled receptors, which in turn enhance the activation of TRPC5 by regulating this channel membrane trafficking. Gq-coupled receptors and TPRC5 are co-expressed in several tissues such as those of the vascular system and in somatosensory neurons, suggesting that this mechanism of TRPC5 activation may have interesting and important implications in arterial pressure sensing and mechanotransduction. |
Sponsor: | The work was supported by grants from the Spanish government (BFU2009-07835 and CONSOLIDER-INGENIO 2010 CSD2007-0023). A-L.C holds a JAE (Junta de Ampliación de Estudios) predoctoral fellowship from the Spanish Research Council, cofinanced by the European Social Fund. |
URI: | http://hdl.handle.net/10045/38820 |
ISSN: | 0031-6768 (Print) | 1432-2013 (Online) |
DOI: | 10.1007/s00424-013-1392-z |
Language: | eng |
Type: | info:eu-repo/semantics/article |
Rights: | The final publication is available at Springer via http://dx.doi.org/10.1007/s00424-013-1392-z |
Peer Review: | si |
Publisher version: | http://dx.doi.org/10.1007/s00424-013-1392-z |
Appears in Collections: | INV - Fisiología de Membranas - Artículos de Revistas INV - FINE - Artículos de Revistas |
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2013_Jemal_etal_PflugersArch_final.pdf | Versión final (acceso restringido) | 995,74 kB | Adobe PDF | Open Request a copy |
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