PIP <sub>2</sub> : A critical regulator of vascular ion channels hiding in plain sight
Osama F. Harraz, David C. Hill‐Eubanks, Mark T. Nelson
Abstract
Significance Phosphatidylinositol 4,5-bisphosphate (PIP 2 ), a plasma membrane lipid, is hydrolyzed by G q -protein–coupled receptor (G q PCR) signaling into inositol 1,4,5-trisphosphate and diacylglycerol—extensively studied second messengers with profound regulatory effects in the vasculature. However, there is extensive evidence that PIP 2 directly regulates ion channels, a finding with significant implications for vascular function. Beyond providing a previously unexplored perspective on how vascular G q PCR signaling influences vascular function, the concept of PIP 2 -mediated ion channel regulation helps to explain how vascular cell excitability is coordinated to support cerebral blood flow control mechanisms. Importantly, the link between the metabolic state of vascular cells and PIP 2 content may provide insight into how metabolism affects vascular ion channel activity and, ultimately, vascular function in health and disease.