Inhibition of native TRPC6 channel activity by phosphatidylinositol 4,5-bisphosphate in mesenteric artery myocytes

Albert, Anthony P. ORCID: https://orcid.org/0000-0002-3596-9634, Saleh, Sohag N. and Large, William A. (2008) Inhibition of native TRPC6 channel activity by phosphatidylinositol 4,5-bisphosphate in mesenteric artery myocytes. Journal of Physiology, 586 (13). pp. 3087-3095. ISSN 0022-3751

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Abstract

The present work investigates the effect of phosphatidylinositol-4,5-bisphosphate (PIP2) on native TRPC6 channel activity in freshly dispersed rabbit mesenteric artery myocytes using patch clamp recording and co-immunoprecipitation methods. Inclusion of 100 μ m diC8-PIP2 in the patch pipette and bathing solutions, respectively, inhibited angiotensin II (Ang II)-evoked whole-cell cation currents and TRPC6 channel activity by over 90%. In inside-out patches diC8-PIP2 also inhibited TRPC6 activity induced by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn -glycerol (OAG) with an IC50 of 7.6 μM. Anti-PIP2 antibodies potentiated Ang II- and OAG-evoked TRPC6 activity by about 2-fold. Depleters of tissue PIP 2 wortmannin and LY294002 stimulated TRPC6 activity, as did the polycation PIP2 scavenger poly-L-lysine. Wortmannin reduced Ang II-evoked TRPC6 activity by over 75% but increased OAG-induced TRPC6 activity by over 50-fold. Co-immunoprecipitation studies demonstrated association between PIP2 and TRPC6 proteins in tissue lysates. Pre-treatment with Ang II, OAG and wortmannin reduced TRPC6 association with PIP2. These results provide for the first time compelling evidence that constitutively produced PIP2 exerts a powerful inhibitory action on native TRPC6 channels.

Item Type:	Article
Uncontrolled Keywords:	physiology ,/dk/atira/pure/subjectarea/asjc/1300/1314
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	29 Oct 2024 09:30
Last Modified:	03 Nov 2024 07:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/97268
DOI:	10.1113/jphysiol.2008.153676

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