Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sodium and chloride channelopathies with myositis: coincidence or connection?

ABSTRACT: A proximal myopathy develops in some patients with muscle channelopathies, but the causative molecular mechanisms are unknown.We reviewed retrospectively all clinical and muscle biopsy findings of 3 patients with channelopathy and additional myositis. Direct DNA sequencing was performed.Pathogenic mutations were identified in each case. Biopsies demonstrated inflammatory infiltrates.Clinicians should consider muscle biopsy in channelopathy patients with severe myalgia and/or subacute weakness and accompanying elevated creatine kinase. Chance association of myositis and channelopathy is statistically unlikely. An alternative hypothesis suggests that inflammatory insults could contribute to myopathy in some patients.

SUBMITTER: Matthews E

PROVIDER: S-EPMC3136616 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Sodium and chloride channelopathies with myositis: coincidence or connection?

Matthews Emma E Miller James A L JA MacLeod Malcolm R MR Ironside James J Ambler Gareth G Labrum Robin R Sud Richa R Holton Janice L JL Hanna Michael G MG

Muscle & nerve 20110622 2

<h4>Introduction</h4>A proximal myopathy develops in some patients with muscle channelopathies, but the causative molecular mechanisms are unknown.<h4>Methods</h4>We reviewed retrospectively all clinical and muscle biopsy findings of 3 patients with channelopathy and additional myositis. Direct DNA sequencing was performed.<h4>Results</h4>Pathogenic mutations were identified in each case. Biopsies demonstrated inflammatory infiltrates.<h4>Conclusions</h4>Clinicians should consider muscle biopsy ...[more]

PMID: 21698652

Similar Datasets

Project description:Epilepsy is a disease characterized by abnormal brain activity and a predisposition to generate epileptic seizures, leading to neurobiological, cognitive, psychological, social, and economic impacts for the patient. There are several known causes for epilepsy; one of them is the malfunction of ion channels, resulting from mutations. Voltage-gated sodium channels (NaV) play an essential role in the generation and propagation of action potential, and malfunction caused by mutations can induce irregular neuronal activity. That said, several genetic variations in NaV channels have been described and associated with epilepsy. These mutations can affect channel kinetics, modifying channel activation, inactivation, recovery from inactivation, and/or the current window. Among the NaV subtypes related to epilepsy, NaV1.1 is doubtless the most relevant, with more than 1500 mutations described. Truncation and missense mutations are the most observed alterations. In addition, several studies have already related mutated NaV channels with the electrophysiological functioning of the channel, aiming to correlate with the epilepsy phenotype. The present review provides an overview of studies on epilepsy-associated mutated human NaV1.1, NaV1.2, NaV1.3, NaV1.6, and NaV1.7.

| S-EPMC7461817 | biostudies-literature

Voltage-gated sodium channels: biophysics, pharmacology, and related channelopathies.

Project description:Voltage-gated sodium channels (VGSC) are multi-molecular protein complexes expressed in both excitable and non-excitable cells. They are primarily formed by a pore-forming multi-spanning integral membrane glycoprotein (α-subunit) that can be associated with one or more regulatory β-subunits. The latter are single-span integral membrane proteins that modulate the sodium current (I(Na)) and can also function as cell adhesion molecules. In vitro some of the cell-adhesive functions of the β-subunits may play important physiological roles independently of the α-subunits. Other endogenous regulatory proteins named "channel partners" or "channel interacting proteins" (ChiPs) like caveolin-3 and calmodulin/calmodulin kinase II (CaMKII) can also interact and modulate the expression and/or function of VGSC. In addition to their physiological roles in cell excitability and cell adhesion, VGSC are the site of action of toxins (like tetrodotoxin and saxitoxin), and pharmacologic agents (like antiarrhythmic drugs, local anesthetics, antiepileptic drugs, and newly developed analgesics). Mutations in genes that encode α- and/or β-subunits as well as the ChiPs can affect the structure and biophysical properties of VGSC, leading to the development of diseases termed sodium "channelopathies". This review will outline the structure, function, and biophysical properties of VGSC as well as their pharmacology and associated channelopathies and highlight some of the recent advances in this field.

| S-EPMC3394224 | biostudies-literature

Channelopathies from mutations in the cardiac sodium channel protein complex.

Project description:The cardiac sodium current underlies excitability in heart, and inherited abnormalities of the proteins regulating and conducting this current cause inherited arrhythmia syndromes. This review focuses on inherited mutations in non-pore forming proteins of sodium channel complexes that cause cardiac arrhythmia, and the deduced mechanisms by which they affect function and dysfunction of the cardiac sodium current. Defining the structure and function of these complexes and how they are regulated will contribute to understanding the possible roles for this complex in normal and abnormal physiology and homeostasis. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".

| S-EPMC3720718 | biostudies-literature

Human voltage-gated sodium channel mutations that cause inherited neuronal and muscle channelopathies increase resurgent sodium currents.

Project description:Inherited mutations in voltage-gated sodium channels (VGSCs; or Nav) cause many disorders of excitability, including epilepsy, chronic pain, myotonia, and cardiac arrhythmias. Understanding the functional consequences of the disease-causing mutations is likely to provide invaluable insight into the roles that VGSCs play in normal and abnormal excitability. Here, we sought to test the hypothesis that disease-causing mutations lead to increased resurgent currents, unusual sodium currents that have not previously been implicated in disorders of excitability. We demonstrated that a paroxysmal extreme pain disorder (PEPD) mutation in the human peripheral neuronal sodium channel Nav1.7, a paramyotonia congenita (PMC) mutation in the human skeletal muscle sodium channel Nav1.4, and a long-QT3/SIDS mutation in the human cardiac sodium channel Nav1.5 all substantially increased the amplitude of resurgent sodium currents in an optimized adult rat-derived dorsal root ganglion neuronal expression system. Computer simulations indicated that resurgent currents associated with the Nav1.7 mutation could induce high-frequency action potential firing in nociceptive neurons and that resurgent currents associated with the Nav1.5 mutation could broaden the action potential in cardiac myocytes. These effects are consistent with the pathophysiology associated with the respective channelopathies. Our results indicate that resurgent currents are associated with multiple channelopathies and are likely to be important contributors to neuronal and muscle disorders of excitability.

| S-EPMC2799199 | biostudies-other

Comparative structural analysis of human Nav1.1 and Nav1.5 reveals mutational hotspots for sodium channelopathies.

Project description:Among the nine subtypes of human voltage-gated sodium (Nav) channels, the brain and cardiac isoforms, Nav1.1 and Nav1.5, each carry more than 400 missense mutations respectively associated with epilepsy and cardiac disorders. High-resolution structures are required for structure-function relationship dissection of the disease variants. We report the cryo-EM structures of the full-length human Nav1.1-β4 complex at 3.3 Å resolution here and the Nav1.5-E1784K variant in the accompanying paper. Up to 341 and 261 disease-related missense mutations in Nav1.1 and Nav1.5, respectively, are resolved. Comparative structural analysis reveals several clusters of disease mutations that are common to both Nav1.1 and Nav1.5. Among these, the majority of mutations on the extracellular loops above the pore domain and the supporting segments for the selectivity filter may impair structural integrity, while those on the pore domain and the voltage-sensing domains mostly interfere with electromechanical coupling and fast inactivation. Our systematic structural delineation of these mutations provides important insight into their pathogenic mechanism, which will facilitate the development of precise therapeutic interventions against various sodium channelopathies.

| S-EPMC7980448 | biostudies-literature

Transport and Electrochemical Characteristics of CJMCED Homogeneous Cation Exchange Membranes in Sodium Chloride, Calcium Chloride, and Sodium Sulfate Solutions.

Project description:Recently developed and produced by Hefei Chemjoy Polymer Material Co. Ltd., homogeneous CJMC-3 and CJMC-5 cation-exchange membranes (CJMCED) are characterized. The membrane conductivity in NaCl, Na2SO4, and CaCl2 solutions, permeability in respect to the NaCl and CaCl2 diffusion, transport numbers, current-voltage curves (CVC), and the difference in the pH (DpH) of the NaCl solution at the desalination compartment output and input are examined for these membranes in comparison with a well-studied commercial Neosepta CMX cation-exchange membrane produced by Astom Corporation, Japan. It is found that the conductivity, CVC (at relatively low voltages), and water splitting rate (characterized by DpH) for both CJMCED membranes are rather close to these characteristics for the CMX membrane. However, the diffusion permeability of the CJMCED membranes is significantly higher than that of the CMX membrane. This is due to the essentially more porous structure of the CJMCED membranes; the latter reduces the counterion permselectivity of these membranes, while allowing much easier transport of large ions, such as anthocyanins present in natural dyes of fruit and berry juices. The new membranes are promising for use in electrodialysis demineralization of brackish water and natural food solutions.

| S-EPMC7463934 | biostudies-literature

Chloride binding site of neurotransmitter sodium symporters.

Project description:Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs have a serine. The LeuT-E290S mutant displays chloride-dependent activity. We show that, in LeuT-E290S cocrystallized with bromide or chloride, the anion is coordinated by side chain hydroxyls from Tyr47, Ser290, and Thr254 and the side chain amide of Gln250. The bound anion and the nearby sodium ion in the Na1 site organize a connection between their coordinating residues and the extracellular gate of LeuT through a continuous H-bond network. The specific insights from the structures, combined with results from substrate binding studies and molecular dynamics simulations, reveal an anion-dependent occlusion mechanism for NSS and shed light on the functional role of chloride binding.

| S-EPMC3666746 | biostudies-literature

catena-Poly[[sodium-di-?-?-d-glucose] chloride].

Project description:The asymmetric unit of the title compound, {[Na(C(6)H(12)O(6))(2)]Cl}(n), contains six glucose mol-ecules, three Na(+) ions and three Cl(-) ions, i.e. three independent {[Na(C(6)H(12)O(6))(2)]Cl} units. Each of these units forms polymeric chains along the c axis. Each Na(+) ion is surrounded by six O atoms from four glucose mol-ecules, forming a distorted octa-hedral geometry. All glucose mol-ecules adopt chair conformations. The constituent units are linked into a three-dimensional framework by O-H?Cl and O-H?O hydrogen bonds, utilizing all the O-H groups.

| S-EPMC2971272 | biostudies-literature

Additive Enhanced Creeping of Sodium Chloride Crystals.

Project description:This article investigates the mechanism behind the creeping of sodium chloride induced by additives. Here, an experimental approach is complemented with theoretical considerations to describe how creeping patterns of brine evolve and how the introduction of additives into the solution affects the morphology of the resultant crystals. We have found that these additives cause kinetic roughening and morphological instability mainly due to the reduction of surface free energy. There was also a marked increase in three-dimensional nucleation of the NaCl crystals and thus branching.

| S-EPMC5465512 | biostudies-literature

Dendrite Pattern Formation of Sodium Chloride Crystal.

Project description:A variety of crystal structures is found in nature, not only equilibrium structures reflecting molecular structures, but also non-equilibrium structures which depend on the physicochemical conditions occurring during the crystal growth. In this paper, we focus on the dendrite structure of sodium chloride (NaCl) formed by the simple evaporation of an aqueous NaCl solution. The characteristics of the growth structures were measured as a function of the initial concentration of NaCl. In addition, the crystal growth process was measured using optical microscopy. As a result, the growth rate was not constant but was found to oscillate over time and synchronize with the wetting of the crystal. Our observations indicate that dendrite structures are more easily generated at higher initial concentrations. The detailed mechanism for dendrite pattern formation is still under investigation.

| S-EPMC8400995 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data