Cerebral Vascular K IR 2.x Channels are Distinctly Regulated by Membrane Lipids and Hemodynamic Forces.

This study examined membrane lipid (phosphatidylinositol‐bis‐phosphate (PIP 2 ) and cholesterol) regulation of cerebral arterial K IR and whether these signaling molecules enable distinct channel pools to uniquely sense hemodynamic forces. Endothelial and smooth muscle cells were freshly isolated from rat cerebral arteries; patch‐clamp electrophysiology, Q‐PCR and immunohistochemistry delineated K IR channel activity and expression. Electrophysiology revealed a Ba 2+ ‐sensitive K IR current in smooth muscle and endothelial cells, while Q‐PCR and immunohistochemistry confirmed K IR 2.x mRNA and protein expression respectively. Each cellular pool of K IR channels was sensitive to particular membrane lipids and hemodynamic forces. Endothelial K IR responded dynamically to PIP 2 manipulations, and laminar flow activated this channel pool in a PIP 2 dependent manner. In contrast, smooth muscle K IR reacted to cholesterol perturbations, and pressure stimuli (e.g. hyposmotic challenge or negative pressure application) modulated this channel pool in a cholesterol dependent manner. The flow and pressure sensitivity of K IR channels was confirmed in intact cerebral arteries using vessel myography. In summary, while both vascular cell types express K IR 2.x channels, each pool is distinctly regulated by membrane lipids and hemodynamic stimuli. This emerging picture of K IR regulation advances our mechanistic understanding of how hemodynamic forces interact to control arterial tone development. Support or Funding Information This research was supported by an operating grant from the Canadian Institute of Health Research. DG Welsh is Rorabeck Chair of Molecular Neuroscience and Vascular Biology at the University of Western Ontario. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .