{"title":"Endothelial inwardly-rectifying K<sup>+</sup> channels as a key component of shear stress-induced mechanotransduction.","authors":"Ibra S Fancher, Irena Levitan","doi":"10.1016/bs.ctm.2020.02.002","DOIUrl":"https://doi.org/10.1016/bs.ctm.2020.02.002","url":null,"abstract":"<p><p>It has been recognized for decades that fluid shear stress plays a major role in vascular function. Acting on the endothelium shear stress induces vasorelaxation of resistance arteries and plays a major role in the propensity of the major arteries to atherosclerosis. Many elements of shear-induced signaling have been identified yet we are just beginning to decipher the roles that mechanosensitive ion channels may play in the signaling pathways initiated by shear stress. Endothelial inwardly-rectifying K<sup>+</sup> channels were identified as potential primary mechanosensors in the late 1980s yet until our recent works, highlighted in the forthcoming chapter, the functional effect of a shear-activated K<sup>+</sup> current was completely unknown. In this chapter, we present the physiological effects of shear stress in arteries in health and disease and highlight the most prevalent of today's investigated mechanosensitive ion channels. Ultimately, we focus on Kir2.1 channels and discuss in detail our findings regarding the downstream signaling events that are induced by shear-activated endothelial Kir2.1 channels. Most importantly, we examine our findings regarding hypercholesterolemia-induced inhibition of Kir channel shear-sensitivity and the impact on endothelial function in the context of flow (shear)-mediated vasodilation and atherosclerosis.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"59-88"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37931607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of ion channels in the microcirculation by mineralocorticoid receptor activation.","authors":"Laura Chambers, Anne M Dorrance","doi":"10.1016/bs.ctm.2020.02.001","DOIUrl":"https://doi.org/10.1016/bs.ctm.2020.02.001","url":null,"abstract":"<p><p>The mineralocorticoid receptor (MR) has classically been studied in the renal epithelium for its role in regulating sodium and water balance and, subsequently, blood pressure. However, the MR also plays a critical role in the microvasculature by regulating ion channel expression and function. Activation of the MR by its endogenous agonist aldosterone results in translocation of the MR into the nucleus, where it can act as a transcription factor. Although most of the actions of the aldosterone can be attributed to its genomic activity though MR activation, it can also act by nongenomic mechanisms. Activation of this ubiquitous receptor increases the expression of epithelial sodium channels (ENaC) in both the endothelium and smooth muscle cells of peripheral and cerebral vessels. MR activation also regulates activity of calcium channels, calcium-activated potassium channels, and various transient receptor potential (TRP) channels. Modification of these ion channels results in a myriad of negative consequences, including impaired endothelium-dependent vasodilation, alterations in generation of myogenic tone, and increased inflammation and oxidative stress. Taken together, these studies demonstrate the importance of studying the impact of the MR on ion channel function in the vasculature. While research in this area has made advances in recent years, there are still many large gaps in knowledge that need to be filled. Crucial future directions of study include defining the molecular mechanisms involved in this interaction, as well as elucidating the potential sex differences that may exist, as these areas of understanding are currently lacking.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"151-185"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.02.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37929670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Boris Martinac, Yury A Nikolaev, Giulia Silvani, Navid Bavi, Valentin Romanov, Yoshitaka Nakayama, Adam D Martinac, Paul Rohde, Omid Bavi, Charles D Cox
{"title":"Cell membrane mechanics and mechanosensory transduction.","authors":"Boris Martinac, Yury A Nikolaev, Giulia Silvani, Navid Bavi, Valentin Romanov, Yoshitaka Nakayama, Adam D Martinac, Paul Rohde, Omid Bavi, Charles D Cox","doi":"10.1016/bs.ctm.2020.08.002","DOIUrl":"https://doi.org/10.1016/bs.ctm.2020.08.002","url":null,"abstract":"<p><p>The rapid progress in mechanobiology has brought together many scientific and engineering disciplines to work hand in hand toward better understanding of the role that mechanical force plays in functioning and evolution of different forms of life. New tools designed by engineers helped to develop new methods and techniques for investigation of mechanical properties of biological cells and tissues. This multidisciplinary approach made it clear that cell mechanics is tightly linked to intracellular signaling pathways, which directly regulate gene expression in response to mechanical stimuli originating outside or inside the cells. Mechanical stimuli act on mechanoreceptors which convert these stimuli into intracellular signals. In this chapter, we review the current knowledge about cell mechanics and the role cell mechanics plays for the function of mechanosensitive ion channels as a special class of mechanoreceptors functioning as molecular transducers of mechanical stimuli on a millisecond timescale.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"83-141"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25576698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of vascular tone by transient receptor potential ankyrin 1 channels.","authors":"Pratish Thakore, Sher Ali, Scott Earley","doi":"10.1016/bs.ctm.2020.01.009","DOIUrl":"https://doi.org/10.1016/bs.ctm.2020.01.009","url":null,"abstract":"<p><p>The Ca<sup>2+</sup>-permeable, non-selective cation channel, TRPA1 (transient receptor potential ankyrin 1), is the sole member of the ankyrin TRP subfamily. TRPA1 channels are expressed on the plasma membrane of neurons as well as non-neuronal cell types, such as vascular endothelial cells. TRPA1 is activated by electrophilic compounds, including dietary molecules such as allyl isothiocyanate, a derivative of mustard. Endogenously, the channel is thought to be activated by reactive oxygen species and their metabolites, such as 4-hydroxynonenal (4-HNE). In the context of the vasculature, activation of TRPA1 channels results in a vasodilatory response mediated by two distinct mechanisms. In the first instance, TRPA1 is expressed in sensory nerves of the vasculature and, upon activation, mediates release of the potent dilator, calcitonin gene-related peptide (CGRP). In the second, work from our laboratory has demonstrated that TRPA1 is expressed in the endothelium of blood vessels exclusively in the cerebral vasculature, where its activation produces a localized Ca<sup>2+</sup> signal that results in dilation of cerebral arteries. In this chapter, we provide an in-depth overview of the biophysical and pharmacological properties of TRPA1 channels and their importance in regulating vascular tone.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"119-150"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.01.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37930118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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":"https://doi.org/10.1016/bs.ctm.2020.01.006","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":0.0,"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":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37930120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Excitability and contractility in arterioles and venules from the urinary bladder.","authors":"Nathan R Tykocki, Frederick C Monson","doi":"10.1016/bs.ctm.2020.01.003","DOIUrl":"https://doi.org/10.1016/bs.ctm.2020.01.003","url":null,"abstract":"<p><p>The urinary bladder performs two key physiological functions: (1) to store urine, and (2) void urine at an appropriate time. While these two functions seem simple, both processes exert prolonged stretch and compressive forces on the urinary bladder vasculature that are greater than those seen by vessels in any other hollow organ. To compensate for these forces, the urinary bladder vasculature has adapted several key features that maintain blood flow during bladder filling and prevent damaging pressure fluctuations during emptying. This chapter first describes key anatomical features of the urinary bladder vasculature and how these features aid in maintaining blood flow in the milieu of the functioning bladder. Next, we investigate the mechanisms regulating excitability of urinary bladder arterioles with emphasis on the development and regulation of myogenic tone. We then discuss the physiological significance and excitability of urinary bladder capillaries and venules, and their important roles in maintaining tissue perfusion. Finally, the functionality of the urinary bladder vasculature will be explored in terms of bladder dysfunction, to understand if lower urinary tract symptoms associated with disease can be considered vascular in nature. Also included are perspectives on the urinary bladder itself as a model for understanding ischemia/reperfusion injury and the possibility that the urinary bladder holds a key to mitigating deleterious effects that result when blood flow is occluded and rapidly restored to other organs.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"301-326"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.01.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37931608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roles of microglial membranes in Alzheimer's disease.","authors":"Jae-Won Shin, James C Lee","doi":"10.1016/bs.ctm.2020.08.007","DOIUrl":"https://doi.org/10.1016/bs.ctm.2020.08.007","url":null,"abstract":"<p><p>The majority of Alzheimer's disease (AD) risk genes are highly and selectively expressed by microglia in the brain. Several of these genes are related to lipid and cholesterol metabolism, lipid synthesis, lipid transport, endocytosis, exocytosis and phagocytosis. Therefore, studying the roles of cellular membrane biophysics in microglial function should improve our understanding of the AD pathology. In this chapter, we discuss how lipid rafts and membrane-cytoskeleton adhesion impact microglial-mediated oxidative stress and clearance of amyloid-β peptide (Aβ). We also discuss potential roles of lipid membrane-bound extracellular vesicles as carriers of pathological factors to promote inflammation and cytotoxicity.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"86 ","pages":"301-314"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.08.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endothelial TRPV4 channels and vasodilator reactivity.","authors":"Yen-Lin Chen, Swapnil K Sonkusare","doi":"10.1016/bs.ctm.2020.01.007","DOIUrl":"https://doi.org/10.1016/bs.ctm.2020.01.007","url":null,"abstract":"<p><p>Transient receptor potential vanilloid 4 (TRPV4) ion channels on the endothelial cell membrane are widely regarded as a crucial Ca<sup>2+</sup> influx pathway that promotes endothelium-dependent vasodilation. The downstream vasodilatory targets of endothelial TRPV4 channels vary among different vascular beds, potentially contributing to endothelial cell heterogeneity. Although numerous studies have examined the role of endothelial TRPV4 channels using specific pharmacological tools over the past decade, their physiological significance remains unclear, mainly due to a lack of endothelium-specific knockouts. Moreover, the loss of endothelium-dependent vasodilation is a significant contributor to vascular dysfunction in cardiovascular disease. The activity of endothelial TRPV4 channels is impaired in cardiovascular disease; therefore, strategies targeting the mechanisms that reduce endothelial TRPV4 channel activity may restore vascular function and provide therapeutic benefit. In this chapter, we discuss endothelial TRPV4 channel-dependent signaling mechanisms, the heterogeneity in endogenous activators and targets of endothelial TRPV4 channels, and the role of endothelial TRPV4 channels in the pathogenesis of cardiovascular diseases. We also discuss potentially interesting future research directions that may provide novel insights into the physiological and pathological roles of endothelial TRPV4 channels.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"85 ","pages":"89-117"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.01.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10337759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}