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Large, William A., Saleh, Sohag N. and Albert, Anthony P. 
ORCID: https://orcid.org/0000-0002-3596-9634
(2009)
Role of phosphoinositol 4,5-bisphosphate and diacylglycerol in regulating native TRPC channel proteins in vascular smooth muscle.
Cell Calcium, 45 (6).
pp. 574-582.
ISSN 0143-4160
Abstract
Stimulation of receptor-operated (ROCs) and store-operated (SOCs) Ca2+-permeable cation channels by vasoconstrictors has many important physiological functions in vascular smooth muscle. The present review indicates that ROCs and SOCs with diverse properties in different blood vessels are likely to be explained by composition of different subunits from the canonical transient receptor potential (TRPC) family of cation channel proteins. In addition we illustrate that activation of native TRPC ROCs and SOCs involves different phospholipase-mediated transduction pathways linked to generation of diacylglycerol (DAG). Moreover we describe recent novel data showing that the endogenous phospholipid phosphoinositol 4,5-bisphosphate (PIP2) has profound and contrasting actions on TRPC ROCs and SOCs. Optimal activation of a native TRPC6 ROC by angiotensin II (Ang II) requires both depletion of PIP2 and generation of DAG which leads to stimulation of TRPC6 via a PKC-independent mechanism. The data also indicate that PIP2 has a marked constitutive inhibitory action of TRPC6 and DAG and PIP2 are physiological antagonists on TRPC6 ROCs. In contrast PIP2 stimulates TRPC1 SOCs and has an obligatory role in activation of these channels by store-depletion which requires PKC-dependent phosphorylation of TRPC1 proteins. Finally, we conclude that interactions between PIP2 bound to TRPC proteins at rest, generation of DAG and PKC-dependent phosphorylation of TRPC proteins have a fundamental role in activation mechanisms of ROCs and SOCs in vascular smooth muscle.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by The Wellcome Trust and the British Heart Foundation. |
| Uncontrolled Keywords: | canonical transient receptor potential channels,diacylglycerol,phosphoinositol 4,5-bisphosphate,vascular smooth muscle,physiology,molecular biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1314 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| 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/97265 |
| DOI: | 10.1016/j.ceca.2009.02.007 |
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