2026-06-29T09:26:24Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1367562026-05-19T23:53:24Zcom_20.500.14352_14col_20.500.14352_15

From cells to organism: impact of dyslipidemia on inwardly rectifying K channels and cerebral vascular function. Kowalewska, Paulina M Sancho González, María Fabris, Sergio Huff, Murray W Gros, Robert Welsh, Donald G 612.8 Arterial spin-labeling MRI Cerebral arteries Electrophysiology Myography Potassium channels Fisiología 2411.11 Neurofisiología Evidence increasingly suggests that dyslipidemia diminishes dilatory function of resistance arteries by altering ion channel activity. Focusing on the cerebral vasculature, this study investigated whether inwardly rectifying K 2.1 (K2.1) channels are targeted early in dyslipidemia. Experiments began at the cellular level (patch-clamp electrophysiology), then progressed to isolated arteries (pressure myography) and whole animals (arterial spin-labeling magnetic resonance imaging). Lipid analysis confirmed dyslipidemia in (normal chow) and C57BL/6 mice fed a high-fat high-cholesterol (HFHC) diet for 8 weeks; no aortic plaques were observed. Patch-clamp electrophysiology revealed a marked reduction in endothelial but not smooth muscle K activity in both dyslipidemic models; this K activity was recoverable by plasma membrane cholesterol depletion. These cellular changes notably diminished flow-induced vasodilation in cerebral arteries isolated from both dyslipidemic models; such deficits were observed in endothelial arteries. A blood pressure challenge induced a perfusion phenotype in HFHC-C57BL/6 but not genetic deletion () mice, consistent with reduced K activity and flow-mediated dilation. Our findings highlight that endothelial K2.1 channels are targeted early in dyslipidemia, which was associated with attenuated flow-mediated dilation in our acute HFHC model. This change likely moderates the range of blood flow control and substrate delivery to active brain tissue. Canadian Institutes of Health Research Heart and Stroke Foundation of Canada Depto. de Fisiología Fac. de Medicina TRUE pub 2026-05-19T09:02:27Z 2026-05-19T09:02:27Z 2025-12-07 journal article VoR https://hdl.handle.net/20.500.14352/136756 XXXX-XXXX 10.1177/0271678X251399019 eng Kowalewska PM, Sancho M, Fabris S, Huff MW, Gros R, Welsh DG. From cells to organism: impact of dyslipidemia on inwardly rectifying K+ channels and cerebral vascular function. J Cereb Blood Flow Metab. 2025 Dec 7:271678X251399019. doi: 10.1177/0271678X251399019. Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ open access application/pdf SAGE