title: Vascular inward rectifier K+ channels as external K+ sensors in the control of cerebral blood flow.
abstract: For decades it has been known that external K(+) ions are rapid and potent vasodilators that increase CBF. Recent studies have implicated the local release of K(+) from astrocytic endfeet-which encase the entirety of the parenchymal vasculature-in the dynamic regulation of local CBF during NVC. It has been proposed that the activation of KIR channels in the vascular wall by external K(+) is a central component of these hyperemic responses; however, a number of significant gaps in our knowledge remain. Here, we explore the concept that vascular KIR channels are the major extracellular K(+) sensors in the control of CBF. We propose that K(+) is an ideal mediator of NVC, and discuss KIR channels as effectors that produce rapid hyperpolarization and robust vasodilation of cerebral arterioles. We provide evidence that KIR channels, of the KIR 2 subtype in particular, are present in both the endothelial and SM cells of parenchymal arterioles and propose that this dual positioning of KIR 2 channels increases the robustness of the vasodilation to external K(+), enables the endothelium to be actively engaged in NVC, and permits electrical signaling through the endothelial syncytium to promote upstream vasodilation to modulate CBF.
authors: Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont, USA.
authors: Thomas A
authors: TA
authors: Longden
authors: Mark T
authors: MT
authors: Nelson
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D000069336:Neurovascular Coupling / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
chemical_list: D024661:Potassium Channels, Inwardly Rectifying
keywords: astrocytic endfoot; capillary; cerebral blood flow; endothelium; functional hyperemia; inward rectifier potassium channel; neurovascular coupling; parenchymal arteriole; smooth muscle
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