Oct 29, 2018

Membrane Lipid-KIR2.x Channel Interactions Enable Hemodynamic Sensing in Cerebral Arteries

BioRxiv : the Preprint Server for Biology
Maria SanchoDonald Gordon Welsh


Inward rectifying (KIR) K+ channels are present in cerebral arterial smooth muscle and endothelial cells, a tandem arrangement suggestive of a dynamic yet undiscovered role for this channel. We explored whether vascular KIR channels were uniquely modulated by membrane lipids and hemodynamic stimuli. A KIR current was isolated in smooth muscle and endothelial cells of rat cerebral arteries and molecular analyses confirmed KIR2.1/KIR2.2 mRNA and protein expression. Electrophysiology next revealed that endothelial KIR was sensitive to phosphatidylinositol 4,5-bisphosphate (PIP2), with depletion impairing flow-induced activation of the channel. In contrast, smooth muscle KIR was sensitive to membrane cholesterol, with sequestration blocking pressure's ability to inhibit this channel. Membrane lipids helped confer KIR mechanosensitivity to intact arteries; virtual models then reconceptualised KIR as a dynamic regulator of basal tone development. We conclude that specific membrane lipid-KIR interactions enable unique channel populations to sense hemodynamic stimuli and set brain perfusion.

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Mentioned in this Paper

KCNJ2 gene
Arterial System
Blood Vessel
Smooth Muscle of Artery
Smooth Muscle
Ion Channel
Phosphatidylinositol 4,5-Diphosphate

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