Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

Pharmacological Reviews, Год журнала: 2021, Номер 73(4), С. 1469 - 1658

Опубликована: Окт. 1, 2021

Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels critical to brain function and centrally implicated numerous psychiatric neurologic disorders. There different classes iGluRs with a variety receptor subtypes each class that play distinct roles neuronal functions. The diversity iGluR subtypes, their unique functional properties roles, has motivated large number studies. Our understanding advanced considerably since first subunit gene was cloned 1989, research focus expanded encompass facets biology have been recently discovered exploit experimental paradigms made possible technological advances. Here, we review insights from more than 3 decades studies an emphasis on progress occurred past decade. We cover structure, function, pharmacology, neurophysiology, therapeutic implications for all assembled subunits encoded 18 genes. SIGNIFICANCE STATEMENT: Glutamate important virtually aspects either involved mediating some clinical features neurological disease or represent target treatment. Therefore, pharmacology this will advance our many at molecular, cellular, system levels provide new opportunities treat patients.

Язык: Английский

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Dental Enamel Formation and Implications for Oral Health and Disease

Physiological Reviews, Год журнала: 2017, Номер 97(3), С. 939 - 993

Опубликована: Май 4, 2017

Dental enamel is the hardest and most mineralized tissue in extinct extant vertebrate species provides maximum durability that allows teeth to function as weapons and/or tools well for food processing. Enamel development mineralization an intricate process tightly regulated by cells of organ called ameloblasts. These heavily polarized form a monolayer around developing move single forming front specified directions they lay down proteinaceous matrix serves template crystal growth. Ameloblasts maintain intercellular connections creating semi-permeable barrier at one end (basal/proximal) receives nutrients ions from blood vessels, opposite (secretory/apical/distal) forms extracellular crystals within pH conditions. In this unique environment, ameloblasts orchestrate growth via multiple cellular activities including modulating transport minerals ions, regulation, proteolysis, endocytosis. many vertebrates, bulk volume first formed subsequently these same retransform their morphology function. Cell death apoptosis regression are fates following maturation, what remain shed during tooth eruption, or incorporated into tooth’s epithelial attachment oral gingiva. review, we examine key aspects dental formation, its developmental genesis ever-increasing wealth data on mechanisms mediating ionic transport, clinical outcomes resulting abnormal ameloblast

Язык: Английский

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Acid-Base Homeostasis

Clinical Journal of the American Society of Nephrology, Год журнала: 2015, Номер 10(12), С. 2232 - 2242

Опубликована: Ноя. 24, 2015

Acid-base homeostasis and pH regulation are critical for both normal physiology cell metabolism function. The importance of this is evidenced by a variety physiologic derangements that occur when plasma either high or low. kidneys have the predominant role in regulating systemic bicarbonate concentration hence, metabolic component acid-base balance. This function has two components: reabsorption virtually all filtered HCO3− production new to replace consumed pathologic acids. generation done net acid excretion. Under conditions, approximately one-third one-half excretion form titratable acid. other two-thirds ammonium. capacity excrete ammonium under conditions loads quantitatively much greater than increase Multiple, often redundant pathways processes exist regulate these renal functions. Derangements homeostasis, however, common clinical medicine can be related systems involved transport kidneys.

Язык: Английский

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A guide to plasma membrane solute carrier proteins

FEBS Journal, Год журнала: 2020, Номер 288(9), С. 2784 - 2835

Опубликована: Авг. 24, 2020

This review aims to serve as an introduction the solute carrier proteins (SLC) superfamily of transporter and their roles in human cells. The SLC currently includes 458 transport 65 families that carry a wide variety substances across cellular membranes. While members this are found throughout organelles, focuses on transporters expressed at plasma membrane. At cell surface, may be viewed gatekeepers milieu, dynamically responding different metabolic states. With altered metabolism being one hallmarks cancer, we also briefly surface play development progression cancer through influence regulating environmental conditions.

Язык: Английский

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Understanding and preventing contrast-induced acute kidney injury

Nature Reviews Nephrology, Год журнала: 2017, Номер 13(3), С. 169 - 180

Опубликована: Янв. 31, 2017

Язык: Английский

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Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Toxics, Год журнала: 2020, Номер 8(4), С. 86 - 86

Опубликована: Окт. 13, 2020

The present review aims to provide an update on health risks associated with the low-to-moderate levels of environmental cadmium (Cd) and lead (Pb) which most populations are exposed. Epidemiological studies examining adverse effects coexposure Cd Pb have shown that may enhance nephrotoxicity vice versa. Herein, existing tolerable intake discussed together conventional urinary threshold limit 5.24 μg/g creatinine. Dietary sources reported for average consumers in U.S., Spain, Korea, Germany China summarized. utility urine, whole blood, plasma/serum, erythrocytes quantify exposure discussed. linked one these measurements chronic kidney disease (CKD) mortality from common ailments reviewed. A level 23.2 μg/day, is less than half safe stated by guidelines, increase risk CKD 73%, one-tenth limit, defined excessive ß2-microglobulin excretion, were increased CKD, heart disease, cancer any site Alzheimer’s disease. These findings indicate current do not adequate protection. Any excretion probably indicative tubular injury. In light evolving realization interaction between Pb, actions minimize toxic metals imperative.

Язык: Английский

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Mechanisms of plant saline-alkaline tolerance

Journal of Plant Physiology, Год журнала: 2023, Номер 281, С. 153916 - 153916

Опубликована: Янв. 10, 2023

Язык: Английский

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Erythrocyte metabolism

Acta Physiologica, Год журнала: 2024, Номер 240(3)

Опубликована: Янв. 25, 2024

Abstract Our aim is to present an updated overview of the erythrocyte metabolism highlighting its richness and complexity. We have manually collected connected available biochemical pathways integrated them into a functional metabolic map. The focus this map on main consisting glycolysis, pentose phosphate pathway, redox metabolism, oxygen purine/nucleoside membrane transport. Other recently emerging are also curated, like methionine salvage glyoxalase system, carnitine lands cycle, as well remnants carboxylic acid metabolism. An additional goal review dynamics providing key numbers used perform basic quantitative analyses. By synthesizing experimental computational data, we conclude that foundations Additionally, can sense levels oxidative stress adjusting mechanics, function. In conclusion, fine‐tuning controls one most important biological processes, is, loading, transport, delivery.

Язык: Английский

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Intracellular pH regulation by acid-base transporters in mammalian neurons

Frontiers in Physiology, Год журнала: 2014, Номер 5

Опубликована: Янв. 1, 2014

Intracellular pH (pHi) regulation in the brain is important both physiological and physiopathological conditions because changes pHi generally result altered neuronal excitability. In this review, we will cover 4 major areas: [1] The effect of on cellular processes brain, including channel activity [2] homeostasis how it determined by balance between rates acid loading (JL) extrusion (JE). JE JL determine steady-state pHi, as well ability cell to defend face extracellular acid-base disturbances (e.g. metabolic acidosis). [3] properties importance members SLC4 SLC9 families transporters expressed that contribute (namely Cl-HCO3 exchanger AE3) (the Na-H exchangers NHE1, NHE3 NHE5 Na+- coupled HCO3- NBCe1, NBCn1, NDCBE, NBCn2). [4] function roles defending under physiopathologic conditions.

Язык: Английский

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Bicarbonate transporters in corals point towards a key step in the evolution of cnidarian calcification

Scientific Reports, Год журнала: 2015, Номер 5(1)

Опубликована: Июнь 4, 2015

Abstract The bicarbonate ion (HCO 3 − ) is involved in two major physiological processes corals, biomineralization and photosynthesis, yet no molecular data on transporters are available. Here, we characterized plasma membrane-type HCO the scleractinian coral Stylophora pistillata . Eight solute carrier (SLC) genes were found genome: five homologs of mammalian-type SLC4 family members three SLC26 members. Using relative expression analysis immunostaining, analyzed cellular distribution these conducted phylogenetic analyses to determine extent conservation among cnidarian model organisms. Our suggest that SLC4γ isoform specific corals responsible for supplying site calcification. Taken together, appears be one key skeleton building which bears profound implications our understanding evolution within cnidarians.

Язык: Английский

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