Physiology of Astroglia

Physiological Reviews, Journal Year: 2017, Volume and Issue: 98(1), P. 239 - 389

Published: Dec. 24, 2017

Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense the central nervous system (CNS). highly heterogeneous in morphological appearance; they express a multitude receptors, channels, membrane transporters. This complement underlies their remarkable adaptive plasticity defines functional maintenance CNS development aging. tightly integrated into networks act within context tissue; astrocytes control at all levels organization from molecular to whole organ.

Language: Английский

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Piezo2 is the major transducer of mechanical forces for touch sensation in mice

Nature, Journal Year: 2014, Volume and Issue: 516(7529), P. 121 - 125

Published: Dec. 1, 2014

Language: Английский

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Ion Channels in Innate and Adaptive Immunity

Annual Review of Immunology, Journal Year: 2015, Volume and Issue: 33(1), P. 291 - 353

Published: March 21, 2015

Ion channels and transporters mediate the transport of charged ions across hydrophobic lipid membranes. In immune cells, divalent cations such as calcium, magnesium, zinc have important roles second messengers to regulate intracellular signaling pathways. By contrast, monovalent sodium potassium mainly membrane potential, which indirectly controls influx calcium cell signaling. Studies investigating human patients with mutations in ion transporters, analysis gene-targeted mice, or pharmacological experiments channel inhibitors revealed ionic signals lymphocyte development innate adaptive responses. We here review mechanisms underlying function lymphocytes cells discuss their development, responses, autoimmunity, well recent efforts develop for immunomodulatory therapy.

Language: Английский

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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men

Physiological Reviews, Journal Year: 2017, Volume and Issue: 98(1), P. 117 - 214

Published: Dec. 6, 2017

The pancreatic β-cell plays a key role in glucose homeostasis by secreting insulin, the only hormone capable of lowering blood concentration. Impaired insulin secretion results chronic hyperglycemia that characterizes type 2 diabetes (T2DM), which currently afflicts >450 million people worldwide. healthy acts as sensor matching its output to circulating It does so via metabolically induced changes electrical activity, culminate an increase cytoplasmic Ca2+ concentration and initiation Ca2+-dependent exocytosis insulin-containing secretory granules. Here, we review recent advances our understanding transcriptome, exocytosis. We highlight salient differences between mouse human β-cells, provide models how different ion channels contribute their activity secretion, conclude discussing these processes become perturbed T2DM.

Language: Английский

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Mechanically Activated Ion Channels

Neuron, Journal Year: 2015, Volume and Issue: 87(6), P. 1162 - 1179

Published: Sept. 1, 2015

Language: Английский

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CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(3), P. 1493 - 1590

Published: May 31, 2018

CLC anion transporters are found in all phyla and form a gene family of eight members mammals. Two proteins, each which completely contains an ion translocation parthway, assemble to homo- or heteromeric dimers that sometimes require accessory β-subunits for function. proteins come two flavors: channels anion/proton exchangers. Structures these protein classes surprisingly similar. Extensive structure-function analysis identified residues involved permeation, anion-proton coupling gating led attractive biophysical models. In mammals, ClC-1, -2, -Ka/-Kb plasma membrane Cl − channels, whereas ClC-3 through ClC-7 2Cl /H + -exchangers endolysosomal membranes. Biological roles CLCs were mostly studied but also plants model organisms like yeast Caenorhabditis elegans. have the control electrical excitability, extra- intracellular homeostasis, transepithelial transport, exchangers influence vesicular composition impinge on endocytosis lysosomal The diverse highlighted by human mouse disorders elicited mutations their genes. These pathologies include neurodegeneration, leukodystrophy, mental retardation, deafness, blindness, myotonia, hyperaldosteronism, renal salt loss, proteinuria, kidney stones, male infertility, osteopetrosis. this review, emphasis is laid cell biological organismal mammalian role disease.

Language: Английский

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Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models

Nature Communications, Journal Year: 2016, Volume and Issue: 7(1)

Published: Aug. 11, 2016

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of proinflammatory cytokine interleukin-1β implicated in many inflammatory diseases. Here we show that several clinically approved widely used NSAIDs fenamate class are effective selective inhibitors via inhibition volume-regulated anion channel macrophages, independently COX Flufenamic acid mefenamic efficacious NLRP3-dependent rodent models inflammation air pouch peritoneum. We also therapeutic effects fenamates using model amyloid beta induced memory loss transgenic mouse Alzheimer’s disease. These data suggest could be repurposed as disease therapeutics.

Language: Английский

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Ion Channels in Cancer: Are Cancer Hallmarks Oncochannelopathies?

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(2), P. 559 - 621

Published: Feb. 7, 2018

Genomic instability is a primary cause and fundamental feature of human cancer. However, all cancer cell genotypes generally translate into several common pathophysiological features, often referred to as hallmarks. Although nowadays the catalog hallmarks quite broad, most obvious them are 1) uncontrolled proliferation, 2) resistance programmed death (apoptosis), 3) tissue invasion metastasis, 4) sustained angiogenesis. Among genes affected by cancer, those encoding ion channels present. Membrane proteins responsible for signaling within among cells, coupling extracellular events with intracellular responses, maintaining ionic homeostasis contribute various extents features each hallmark. Moreover, tight association these channel dysfunction gives good reason classify special type channelopathies, namely oncochannelopathies. relation differs from classical definition disease states causally linked inherited mutations that alter channel's biophysical properties, in broader context state, which pathogenesis essentially contribute, such classification seems absolutely appropriate. In this review authors provide arguments substantiate point view.

Language: Английский

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VRACs and other ion channels and transporters in the regulation of cell volume and beyond

Nature Reviews Molecular Cell Biology, Journal Year: 2016, Volume and Issue: 17(5), P. 293 - 307

Published: April 1, 2016

Language: Английский

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Physiological role of taurine – from organism to organelle

Acta Physiologica, Journal Year: 2014, Volume and Issue: 213(1), P. 191 - 212

Published: Aug. 20, 2014

Taurine is often referred to as a semi-essential amino acid newborn mammals have limited ability synthesize taurine and rely on dietary supply. not thought be incorporated into proteins no aminoacyl tRNA synthetase has yet been identified oxidized in mammalian cells. However, contributes significantly the cellular pool of organic osmolytes accordingly acknowledged for its role cell volume restoration following osmotic perturbation. This review describes homeostasis cells organelles with emphasis biophysics/membrane dynamics, regulation transport involved active uptake passive release well physiological processes, example, development, lung function, mitochondrial antioxidative defence apoptosis which seem affected by shift expression transporters and/or content.

Language: Английский

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