PIP<sub>2</sub>: A critical regulator of vascular ion channels hiding in plain sight.

Harraz, Osama F; Hill-Eubanks, David; Nelson, Mark T · Proc Natl Acad Sci U S A · 2020

review · Level V

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Abstract

The phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>), has long been established as a major contributor to intracellular signaling, primarily by virtue of its role as a substrate for phospholipase C (PLC). Signaling by G<sub>q</sub>-protein-coupled receptors triggers PLC-mediated hydrolysis of PIP<sub>2</sub> into inositol 1,4,5-trisphosphate and diacylglycerol, which are well known to modulate vascular ion channel activity. Often overlooked, however, is the role PIP<sub>2</sub> itself plays in this regulation. Although numerous reports have demonstrated that PIP<sub>2</sub> is critical for ion channel regulation, how it impacts vascular function has received scant attention. In this review, we focus on PIP<sub>2</sub> as a regulator of ion channels in smooth muscle cells and endothelial cells-the two major classes of vascular cells. We further address the concerted effects of such regulation on vascular function and blood flow control. We close with a consideration of current knowledge regarding disruption of PIP<sub>2</sub> regulation of vascular ion channels in disease.

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