{"title":"K<sub>IR</sub> channels in the microvasculature: Regulatory properties and the lipid-hemodynamic environment.","authors":"Maria Sancho, Donald G Welsh","doi":"10.1016/bs.ctm.2020.01.006","DOIUrl":null,"url":null,"abstract":"<p><p>Basal tone and perfusion control is set in cerebral arteries by the sensing of pressure and flow, key hemodynamic stimuli. These forces establish a contractile foundation within arterial networks upon which local neurovascular stimuli operate. This fundamental process is intimately tied to arterial V<sub>M</sub> and the rise in cytosolic [Ca<sup>2+</sup>] by the graded opening of voltage-operated Ca<sup>2+</sup> channels. Arterial V<sub>M</sub> is in turn controlled by a dynamic interaction among several resident ion channels, K<sub>IR</sub> being one of particular significance. As the name suggests, K<sub>IR</sub> displays strong inward rectification, retains a small outward component, potentiated by extracellular K<sup>+</sup> and blocked by micromolar Ba<sup>2+</sup>. Cerebrovascular K<sub>IR</sub> is unique from other K<sup>+</sup> currents as it is present in both smooth muscle and endothelium yet lacking in classical regulatory modulation. Such observations have fostered the view that K<sub>IR</sub> is nothing more than a background conductance, activated by extracellular K<sup>+</sup> and which passively facilitates dilation. Recent work in cell model systems has; however, identified two membrane lipids, phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>) and cholesterol, that interact with K<sub>IR</sub>2.x, to stabilize the channel in the preferred open or silent state, respectively. Translating this unique form of regulation, recent studies have demonstrated that specific lipid-protein interactions enable unique K<sub>IR</sub> populations to sense distinct hemodynamic stimuli and set basal tone. This review summarizes the current knowledge of vascular K<sub>IR</sub> channels and how the lipid and hemodynamic impact their activity.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"227-259"},"PeriodicalIF":0.0000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.01.006","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in membranes","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.ctm.2020.01.006","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/2/21 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 3
Abstract
Basal tone and perfusion control is set in cerebral arteries by the sensing of pressure and flow, key hemodynamic stimuli. These forces establish a contractile foundation within arterial networks upon which local neurovascular stimuli operate. This fundamental process is intimately tied to arterial VM and the rise in cytosolic [Ca2+] by the graded opening of voltage-operated Ca2+ channels. Arterial VM is in turn controlled by a dynamic interaction among several resident ion channels, KIR being one of particular significance. As the name suggests, KIR displays strong inward rectification, retains a small outward component, potentiated by extracellular K+ and blocked by micromolar Ba2+. Cerebrovascular KIR is unique from other K+ currents as it is present in both smooth muscle and endothelium yet lacking in classical regulatory modulation. Such observations have fostered the view that KIR is nothing more than a background conductance, activated by extracellular K+ and which passively facilitates dilation. Recent work in cell model systems has; however, identified two membrane lipids, phosphatidylinositol 4,5-bisphosphate (PIP2) and cholesterol, that interact with KIR2.x, to stabilize the channel in the preferred open or silent state, respectively. Translating this unique form of regulation, recent studies have demonstrated that specific lipid-protein interactions enable unique KIR populations to sense distinct hemodynamic stimuli and set basal tone. This review summarizes the current knowledge of vascular KIR channels and how the lipid and hemodynamic impact their activity.
期刊介绍:
Current Topics in Membranes provides a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. Each volume is a guest edited compendium of membrane biology.