• It defines molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. (wikipedia.org)
  • The N-terminal, cytoplasmic tetramerization domain (T1) of voltage-gated potassium channels encodes molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. (wikipedia.org)
  • We report a case of congenital LQT2 with potassium voltage-gated channel subfamily H member 2 gene ( KCNH2 ) mutation misdiagnosed as refractory epilepsy and treated with various AEDs for 22 years. (biomedcentral.com)
  • Diagnosis of LQTS type 2 (LQT2) was confirmed by ECG and the detection of potassium voltage-gated channel subfamily H member 2 gene ( KCNH2 ) mutation and epilepsy was ruled out and all AEDs were withdrawn based on her normal 24-h video electroencephalograph (VEEG) monitoring. (biomedcentral.com)
  • Homo sapiens potassium voltage-gated channel subfamily A regulatory beta subunit 2 (KCNAB2), transcript variant 2, mRNA. (ucsc.edu)
  • This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. (ucsc.edu)
  • Potassium two pore domain channel subfamily K member 16 is encoded by the gene KCNK16. (antibodiesinc.com)
  • This gene encodes a sodium-activated potassium channel subunit which is thought to function in ion conductance and developmental signaling pathways. (nih.gov)
  • Structurally, the pore-forming subunit of K ir channels is the α-subunit. (tocris.com)
  • Coexpression of SUR2 and the inward rectifier K+ channel subunit Kir6.2 in COS1 cells reconstitutes the properties of K(ATP) channels described in cardiac and skeletal muscle. (nih.gov)
  • Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. (ox.ac.uk)
  • Because ATP-sensitive potassium (K(ATP)) channels mediate glucose-stimulated insulin secretion from the pancreatic beta cells, we hypothesized that activating mutations in the gene encoding the Kir6.2 subunit of this channel (KCNJ11) cause neonatal diabetes. (ox.ac.uk)
  • One beta subunit, produced from the KCNE1 gene, binds to the channel and regulates its activity. (medlineplus.gov)
  • Ehmke H. Physiological functions of the regulatory potassium channel subunit KCNE1. (medlineplus.gov)
  • Structural and functional characterization of human potassium channel subunit beta 1 (KCNA1B). (nih.gov)
  • Accessory potassium channel protein which modulates the activity of the pore-forming alpha subunit. (ucsc.edu)
  • Belongs to the shaker potassium channel beta subunit family. (ucsc.edu)
  • Homo sapiens potassium channel tetramerization domain containing 14 (KCTD14), transcript variant 1, mRNA. (origene.com)
  • KCNT1 encodes a sodium-activated potassium (KNa) channel that is highly expressed in the nervous system. (nature.com)
  • Mice homozygous for a dominant negative knock-in mutation in this gene exhibit partial prenatal lethality and abnormal afterhyperpolarization in the in the CA3 area of hippocampus. (jax.org)
  • We, therefore, identified the first genetic defect in THypoKPP, a mutation in the KCNE3 gene. (unifesp.br)
  • When the most common mutation in Kir6.2 was coexpressed with sulfonylurea receptor 1 in Xenopus laevis oocytes, the ability of ATP to block mutant K(ATP) channels was greatly reduced. (ox.ac.uk)
  • A small percentage of cases of acquired long QT syndrome occur in people who have an underlying mutation in the KCNE1 gene. (medlineplus.gov)
  • Our previous study reported two unrelated patients with EIFMS caused by a de novo missense mutation at the pore region of the KCNT1 channel. (nature.com)
  • The genetic alteration causative of SCAN-1 is a mutation altering the function of a gene called tdp1 (tyrosyl- DNA phosphodiesterase 1). (ataxia.org)
  • For example, the T8K mutation affects the N-terminal, which is the part of the channel involved in membrane transport and interacting with other proteins. (genomeweb.com)
  • Cystic fibrosis (CF) is an autosomal recessive condition caused by the mutation of the cystic fibrosis trans-membrane regulator gene (CFTR) on chromosome 7. (who.int)
  • All K+ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). (wikipedia.org)
  • K+ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. (wikipedia.org)
  • In addition, there are K+ channel alpha-subunits that possess two P-domains. (wikipedia.org)
  • These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity. (wikipedia.org)
  • The KCNE1 protein regulates a channel made up of four parts, called alpha subunits, which are produced from the KCNQ1 gene. (medlineplus.gov)
  • The Kv2 family of voltage-gated potassium channel α subunits, comprising Kv2.1 and Kv2.2, mediate the bulk of the neuronal delayed rectifier K + current in many mammalian central neurons. (jneurosci.org)
  • We expressed chimeric channels composed of different components of the Kv7.4 and Kv7.5 α -subunits in vascular smooth muscle cells to determine which components are essential for enhancement or inhibition of channel activity. (aspetjournals.org)
  • The present studies identify distinct functional domains that confer differential sensitivities of Kv7.4 and Kv7.5 to stimulatory and inhibitory signaling and reveal structural features of the channel subunits that determine their biophysical properties. (aspetjournals.org)
  • functional channels form as homo- or hetero-tetramers of α -subunits ( Delmas and Brown, 2005 ). (aspetjournals.org)
  • Functional and molecular aspects of voltage-gated K+ channel beta subunits. (nih.gov)
  • Multiple genetic variations in sodium channel subunits in a case of sudden infant death syndrome. (cdc.gov)
  • K+ channel tetramerisation domain is the N-terminal, cytoplasmic tetramerisation domain (T1) of voltage-gated K+ channels. (wikipedia.org)
  • R83H was recently found in two FHypoKPP unrelated families, in which the mutant decreased outward potassium flux, resulting in a more positive resting membrane potential. (unifesp.br)
  • The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential. (wikipedia.org)
  • During the generation of action potentials, sodium ions move across the membrane through voltage-gated ion channels. (medscape.com)
  • The resting muscle fiber membrane is polarized primarily by the movement of chloride through chloride channels and is repolarized by movement of potassium. (medscape.com)
  • Ion channel dysfunction is usually well compensated with normal excitation, and additional triggers are often necessary to produce muscle inexcitability owing to sustained membrane depolarization. (medscape.com)
  • Inwardly rectifying potassium channels, such as Kir2.6, maintain resting membrane potential in excitable cells and aid in repolarization of cells following depolarization. (wikipedia.org)
  • Neurons of different cortical layers express diverse populations of ion channels and possess distinct intrinsic membrane properties. (jneurosci.org)
  • Kv7 family channels mediate a voltage-dependent outward flux of potassium ions, which contributes to the establishment of negative membrane potentials in many cell types. (aspetjournals.org)
  • KCNK3, the researchers noted, encodes part of a potassium channel that is thought to be involved in resting membrane potential and pulmonary vascular tone. (genomeweb.com)
  • sults: sodium 133 mmol/L, potassium membrane regulator gene ( CFTR ) on He was readmitted 5 more times 3.4 mmol/L, chloride 100 mmol/L and chromosome 7. (who.int)
  • The inward-rectifier potassium channel family (also known as 2-TM channels) include the strong inward-rectifier channels (K ir 2.x), the G-protein-activated inward-rectifier channels (K ir 3.x) and the ATP-sensitive channels (K ir 6.x), which combine with sulphonylurea receptors. (tocris.com)
  • The Kir2.6 also known as inward rectifier potassium channel 18 is a protein that in humans is encoded by the KCNJ18 gene. (wikipedia.org)
  • This new molecule has been shown to interact with the ROMK gene and then inhibit the excretion of potassium, thus causing high blood levels. (scienceblog.com)
  • These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. (wikipedia.org)
  • The authors' findings, published online this week by the peer-reviewed journal Nature Medicine , suggest that mutations of either of two gene products -- proteins called KCNE2 and KCNQ1 -- already known to be involved in human cardiac arrhythmias, could also cause thyroid dysfunction. (sciencedaily.com)
  • While we have identified KCNQ1 and KCNE2 in both mouse and human thyroid, much additional work is required before we can fully understand how inherited mutations in the genes coding these proteins affect human thyroid function, how this in turn influences the health of human heart and other tissues, and how useful our discoveries will be in developing therapies to treat thyroid and thyroid-related human disease," explains Dr. Abbott. (sciencedaily.com)
  • Many of these genes encode proteins (e.g., enzymes involved in protein glycosylation) rarely associated with viruses. (uml.edu)
  • GXD's primary emphasis is on endogenous gene expression during development. (jax.org)
  • The gene encoding the voltage-gated potassium channel Kv1.1, KCNA1, was codon-optimized for human expression and mutated to accelerate the channels' recovery from inactivation. (ucl.ac.uk)
  • This demonstration of efficacy in a clinically relevant setting, combined with the improved safety conferred by cell type-specific expression and integration-deficient delivery, identify EKC gene therapy as ready for clinical translation in the treatment of refractory focal epilepsy.SIGNIFICANCE STATEMENTPharmacoresistant epilepsy affects up to 0.3% of the population. (ucl.ac.uk)
  • such motifs have also been reported to destabilize the messages of many other genes and might therefore shorten the life of the 4.5-kb transcript during its natural expression. (okstate.edu)
  • The expression of channels in bacteria was confirmed by RT-PCR. (york.ac.uk)
  • Our results show that expression of these channels in the bacterial mutant restored the LB2003 growth on low K + media. (york.ac.uk)
  • Isayenkov, SV & Maathuis, FJM 2015, ' The expression of rice vacuolar TPK channels genes restores potassium uptake in E. coli mutant strain LB2003 ', Cytology and Genetics , vol. 49, no. 1, pp. 1-5. (york.ac.uk)
  • Lundquist AL, Turner CL, Ballester LY, George AL Jr. Expression and transcriptional control of human KCNE genes. (medlineplus.gov)
  • To understand the molecular-genetic basis of functional specialization and identify potential drug targets specific to each neuron subtype, we performed a genome wide assessment of both gene expression and splicing across EXC, PV, SST and VIP neurons from male and female mouse brains. (jneurosci.org)
  • These results reveal numerous examples where neuron subtype-specific gene expression, as well as splice-isoform usage, can explain functional differences between neuron subtypes, including in presynaptic plasticity, postsynaptic receptor function, and synaptic connectivity specification. (jneurosci.org)
  • We provide a searchable web resource for exploring differential mRNA expression and splice form usage between excitatory, PV, SST, and VIP neurons ( http://research-pub.gene.com/NeuronSubtypeTranscriptomes ). (jneurosci.org)
  • This resource, combining a unique new dataset and novel application of analysis methods to multiple relevant datasets, identifies numerous potential drug targets for manipulating circuit function, reveals neuron subtype-specific roles for disease-linked genes, and is useful for understanding gene expression changes observed in human patient brains. (jneurosci.org)
  • We used a genome-wide analysis which not only examined differential gene expression levels but could also detect differences in splice isoform usage. (jneurosci.org)
  • More recently, increased expression of NOTCH pathway genes was implicated in some DIPGs and NOTCH path inhibition contributed to reduced tumor growth in culture 14 , but the specificity of these treatments for H3.3 mutant cells remains unclear. (nature.com)
  • Expression and Activity of Methionine Cycle Genes Are Altered Following Folate and Vitamin E Deficiency Under Oxidative Challenge: Modulation by Apolipoprotein E-Deficiency. (uml.edu)
  • This focuses on the expression of the human tdp1 mutant gene in brain tissue of flies lacking the endogenous Gkt protein. (ataxia.org)
  • More interestingly, a large number of noncoding fragments were found in peripheral blood cells of patients with asthma, including natural antisense chains, pseudogenes, and differential expression of ncRNA between genes [ 14 ]. (hindawi.com)
  • In addition, Th2 cells are important mediators of type I allergy, and it has been reported that ncRNA promotes Th2 cell migration to target organs by regulating chemokine gene expression [ 17 ]. (hindawi.com)
  • The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. (bvsalud.org)
  • Total RNA from tumors the expression of thousands of genes (3) to address complex questions was isolated using two successive rounds of Trizol. (lu.se)
  • Search on a gene symbol or gene name keyword(s). (jax.org)
  • and nondihydropyridine (eg, verapamil) and dihydropyridine (eg, nifedipine) calcium channel blockers. (medscape.com)
  • FHypoKPP is caused by mutations in ionic channel genes calcium (CACNIAS), sodium (SCN4A) and potassium (KCNE3). (unifesp.br)
  • and three types of calcium (Ca)-activated K+ channels (BK, IK and SK). (wikipedia.org)
  • Discussion in this article primarily addresses the sodium, calcium, and potassium channelopathies as well as secondary forms of PP. Chloride channelopathies are not associated with episodic weakness and are discussed in more detail in the articles on myotonic disorders. (medscape.com)
  • Catheterization is also performed to determine pulmonary vasoreactivity, which can be prognostic and figures in the initiation and titration of high-dose calcium channel blocker (CCB) therapy. (medscape.com)
  • The ion channels affected include those responsible for the inward sodium or calcium currents and those responsible for the outward potassium current. (msdmanuals.com)
  • Long-term treatment improves the quality of life and survival rate in patients who are proven responders to calcium channel blockers (CCBs). (medscape.com)
  • He underwent fluid resuscitation and investigations showed the following results: serum sodium 128 mmol/L, chloride 76 mmol/L, potassium 3.3 mmol/L, bicarbonate 28 mmol/L, anion gap 15.6 mmol/L, urea 35 mg/dL, creatinine 1.3 mg/dL, calcium 10.5 mg/dL, phosphorus 7.6mg/dL and magnesium 2.3 mg/dL. (who.int)
  • The gene encoding the inwardly rectifying potassium channel Kir4.1 may be involved in sudden infant death syndrome. (cdc.gov)
  • Gene Dosage in the Dysbindin Schizophrenia Susceptibility Network Differentially Affect Synaptic Function and Plasticity. (tcd.ie)
  • Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. (nih.gov)
  • Thus, transcriptional and post-transcriptional regulation of mKv1.4, coupled with selective usage of the two alternate Kv1.4 mRNAs, may modulate the levels of functional Kv1.4 channels. (okstate.edu)
  • In order to further evaluate the functional features of these channels, two of the three rice isoforms and one Arabidopsis isoform (AtTPK1) were cloned and expressed in the mutant E. coli strain-LB2003. (york.ac.uk)
  • Our data suggest that these plant vacuolar channels can form functional potassium transport systems in bacterial cells. (york.ac.uk)
  • Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. (ucsc.edu)
  • This member alters functional properties of the KCNA4 gene product. (ucsc.edu)
  • These channels, which transport positively charged potassium atoms (ions) into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals. (medlineplus.gov)
  • These channels are active in the inner ear and in heart (cardiac) muscle, where they transport potassium ions out of cells. (medlineplus.gov)
  • An altered KCNE1 protein cannot regulate the flow of potassium ions through channels in the inner ear and cardiac muscle. (medlineplus.gov)
  • Here we report successful gene editing of H3.3K27M and G34R point mutations in human normal brain and pediatric glioma cells, generating pairs of otherwise isogenic cell lines that allowed us to define epigenetic and transcriptomic changes contributing to gliomagenesis in the native genomic context. (nature.com)
  • This record is derived from a genomic sequence (NW_014804967.1) annotated using gene prediction method: Gnomon, supported by mRNA and EST evidence. (genscript.com)
  • Anti-Ro/SSA antibodies may produce a long QT interval syndrome by inhibiting the human ether-a-go-go-related gene ( hERG ) related outward potassium channel, and transplacental exposure to these antibodies in utero is responsible for congenital AV block. (msdmanuals.com)
  • About 10 percent of cases are caused by mutations in this gene. (medlineplus.gov)
  • Hypokalemic Periodic Paralyses comprise diverse diseases characterized by acute and reversible attacks of severe muscle weakness, associated with low serum potassium. (unifesp.br)
  • the altered potassium metabolism is a result of the PP. In primary and thyrotoxic PP, flaccid paralysis occurs with relatively small changes in the serum potassium level, whereas in secondary PP, serum potassium levels are markedly abnormal. (medscape.com)
  • Blue squares indicate phenotypes directly attributed to mutations/alleles of this gene. (jax.org)
  • These results identify a molecular mechanism that contributes to heterogeneity in cortical neuron ion channel function and regulation. (jneurosci.org)
  • Molecular site of action of the antiarrhythmic drug propafenone at the voltage-operated potassium channel Kv2.1. (nih.gov)
  • A series of 172 molecular structures that block the hERG K + channel were used to develop a classification model where, initially, eight types of PaDEL fingerprints were used for k -nearest neighbor model development. (springer.com)
  • They have identified a new molecular pathway and a new class of molecules responsible for preventing potassium from being excreted normally through the kidney. (scienceblog.com)
  • Currently, there are no drugs that specifically target the molecular defect in kidney potassium retention. (scienceblog.com)
  • Genetic investigations of sudden unexpected deaths in infancy using next-generation sequencing of 100 genes associated with cardiac diseases. (cdc.gov)
  • Mutations in this gene cause the early-onset epileptic disorders, malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy. (nih.gov)
  • Mutations in this gene have been linked to thyrotoxic periodic paralysis. (wikipedia.org)
  • NEW YORK (GenomeWeb News) - A team led by researchers at Columbia University Medical Center uncovered a new gene linked with pulmonary arterial hypertension, and as the group reported in The New England Journal of Medicine this week, the effects of some mutations in this gene may be mitigated by drug treatment. (genomeweb.com)
  • Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). (ucsc.edu)
  • Role of the S2 and S3 segment in determining the activation kinetics in Kv2.1 channels. (nih.gov)
  • METHODS: We sequenced the KCNJ11 gene in 29 patients with permanent neonatal diabetes. (ox.ac.uk)
  • CONCLUSIONS: Heterozygous activating mutations in the gene encoding Kir6.2 cause permanent neonatal diabetes and may also be associated with developmental delay, muscle weakness, and epilepsy. (ox.ac.uk)
  • The human ether-a-go-go related gene (hERG, KCNH2) encodes for a voltage dependent K + ion channel (Kv11.1). (springer.com)
  • Samples were also negative for antibodies against Hu, Ri, Yo, and voltage-gated potassium channel antigens. (cdc.gov)
  • The rice genome encodes three different isoforms of two pore potassium channels (TPKs). (york.ac.uk)
  • While studying mice that had the KCNE2 gene removed from their genome, the researchers observed that the animals developed symptoms of hypothyroidism, especially during pregnancy, and gave birth to pups with dwarfism, alopecia (baldness) and cardiomegaly (enlarged heart). (sciencedaily.com)
  • When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions. (wikipedia.org)
  • Analysis of two highly expressed genes from Chlorella virus PBCV-1: Protein characterization and the DNA sequences of the major capsid protein gene and the early/late 33-kDa protein gene. (uml.edu)
  • H3.3 mutant gliomas are also particularly sensitive to NOTCH pathway gene knockdown and drug inhibition, reducing their viability in culture. (nature.com)
  • A mouse model study implicated alterations in bivalent genes in mutant H3.3 downstream function 20 . (nature.com)
  • Taken together, our findings suggest striking overlap between putative mechanisms of K27M and G34R mutations and point to increased NOTCH signaling playing a key role in K27M-related gliomagenesis, resulting from aberrant gene derepression due to impaired H3K27me3 deposition at super-enhancers in H3.3 mutant cells. (nature.com)
  • Through electrophysiological studies of mutant KCNK3 potassium channels, the researchers found that all six variants led to changes to the channel and a loss of its function. (genomeweb.com)
  • To try to rescue the effects of these mutations, Chung and her colleagues turned to a phospholipase A2 inhibitor that had previously been shown to activate non-mutant KCNK3 channels. (genomeweb.com)
  • In cell cultures, they found that the application of phospholipase A2 inhibitor ONO-RS-082 could increase the current density of two of the three mutant channels tested to non-mutant levels, suggesting a possible therapeutic for some PAH patients. (genomeweb.com)
  • Click on a disease name to see all genes associated with that disease. (jax.org)
  • The patient has never been suspected LQTS because her normal routine 12 channel electrocardiograph (ECG) at early disease stage, until we caught clinical attacks during her initial visit to our emergency room (ER) and documented simultaneous cardiac arrhythmia. (biomedcentral.com)
  • 4 These findings suggested that KCNT1 is the major disease-associated gene for the EIFMS phenotype. (nature.com)
  • These findings may improve our understanding of the roles of these channels in smooth muscle physiology and disease, particularly in conditions where Kv7.4 and Kv7.5 are differentially expressed. (aspetjournals.org)
  • This new class of drugs will pave the way to allow damaged kidneys from long-standing high blood pressure, diabetes or heart disease, to continue to properly excrete potassium in the urine, so that potentially fatal hyperkalemia can be prevented. (scienceblog.com)
  • People at highest risk for abnormally high levels of potassium in the blood are those with kidney disease because they cannot properly excrete the potassium through the urine. (scienceblog.com)
  • In people with kidney disease, the protein made by this gene no longer signals properly to ensure adequate excretion through the urine, so the potassium can build up in the blood. (scienceblog.com)
  • Our findings solve a mystery of how potassium excretion is turned off in response to dietary potassium deficiency and points to an underlying defect in kidney disease" says Dr. Fang. (scienceblog.com)
  • E. Albert Reece, MD, PhD, MBA, Vice President for Medical Affairs, University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine, says these findings change our basic understanding of how potassium balance is maintained in the body and is critical in the care of patients with kidney disease from conditions such as diabetes. (scienceblog.com)
  • And while a number of genes have been linked to familial and idiopathic PAH, the genetic cause of about a quarter of familial cases of the disease is unknown. (genomeweb.com)
  • In genetics, it's common to identify a gene that is the source of a disease. (genomeweb.com)
  • Of those, the G203D missense variant in KCNK3 stood out to the researchers as a strong disease-causing variant as the gene encodes a potassium channel. (genomeweb.com)
  • In a Novartis-sponsored study in the New England Journal of Medicine, researchers found that a CRISPR-Cas9-based treatment targeting promoters of genes encoding fetal hemoglobin could reduce disease symptoms. (genomeweb.com)
  • Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations. (lu.se)
  • The C-terminal cytoplasmic domain of KCNT1 interacts with a protein network, including the Fragile X mental retardation protein, thus stimulating the KCNT1 channel. (nature.com)
  • 3 reported that mutations in the cytoplasmic C-terminal domain lead to constitutive activation of the KCNT1 channel. (nature.com)
  • In the heart, the channels are involved in recharging the cardiac muscle after each heartbeat to maintain a regular rhythm. (medlineplus.gov)
  • Genes previously known to be essential to the coordinated, rhythmic electrical activity of cardiac muscle -- a healthy heartbeat -- have now also been found to play a key role in thyroid hormone (TH) biosynthesis, according to researchers. (sciencedaily.com)
  • KCNQ1 and KCNE2 were each recognized more than a decade ago as forming potassium channels in cardiac muscle that help end each heartbeat in a timely fashion. (sciencedaily.com)
  • CRISPR/Cas9-mediated Knockout of the Neuropsychiatric Risk Gene KCTD13 Causes Developmental Deficits in Human Cortical Neurons Derived from Induced Pluripotent Stem Cells. (nih.gov)
  • We have developed a gene therapy that builds on a mechanistic understanding of altered neuronal and circuit excitability in cortical epilepsy. (ucl.ac.uk)
  • in 15 patients with THypoKPP, using target-exon PCR, CSGE screening, and direct sequencing, we excluded known mutations in CACNIAS and SCN4A genes. (unifesp.br)
  • With HyperPP fast channel inactivation, mutations are usually situated in the inner parts of transmembrane segments or in the intracellular loops affecting the docking sites for the fast inactivating particle, thus impairing fast channel inactivation leading to persistent Na + current. (medscape.com)
  • The prominence of Kv7 channels as regulators of electrical excitability may be ascribed to their unique properties, such as a very negative threshold of activation (negative to −50 mV), absence of time-dependent inactivation, and high sensitivity to signal transduction pathways that influence their probability of opening, either positively or negatively ( Delmas and Brown, 2005 ). (aspetjournals.org)
  • Reduced K+ channel inactivation, spike broadening, and after-hyperpolarization in Kvbeta1.1-deficient mice with impaired learning. (nih.gov)
  • Voltage-sensitive ion channels closely regulate generation of action potentials (brief and reversible alterations of the voltage of cellular membranes). (medscape.com)
  • This is because Drosophila genes controlling fundamental cellular functions, such as cell growth and death, are quite identical to those found in human cells. (ataxia.org)
  • Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. (ucsc.edu)
  • Candidate gene variants of the immune system and sudden infant death syndrome. (cdc.gov)
  • Ali H, Olatubosun A, Vihinen M. Classification of mismatch repair gene missense variants with PON-MMR. (lu.se)
  • Gene therapy represents a promising alternative, but treating epilepsy in this way involves irreversible changes to brain tissue, so vector design must be carefully optimized to guarantee safety without compromising efficacy. (ucl.ac.uk)
  • We set out to develop an epilepsy gene therapy vector optimized for clinical translation. (ucl.ac.uk)
  • When packaged into an adeno-associated viral vector (AAV2/9), the EKC gene was also effective at suppressing seizures in a male rat model of temporal lobe epilepsy. (ucl.ac.uk)
  • Adeno-associated viral delivery of the channel to both hippocampi was also effective in a model of temporal lobe epilepsy. (ucl.ac.uk)
  • In epilepsy, several gene therapy alternatives are at late preclinical stage, and their advance towards clinical trials is expected in the nearest future. (lu.se)
  • In this proposal, we will investigate a new generation of precise gene therapies based on targeting novel optogenetic and chemogenetic tools to strengthen seizure-suppressant effect and improve seizure freedom outcome in drug-resistant models of epilepsy. (lu.se)
  • Taken together, these innovative approaches will lead to discovery of novel gene therapy targets and modalities, facilitating preclinical investigations, which in the long-run will benefit drug-resistant population of patients with epilepsy. (lu.se)
  • However, agitoxin 2 differs significantly from the other channel blockers in the specificity of its interactions. (rcsb.org)
  • A recent report on the use of PaDEL fingerprints in conjunction with a k -NN strategy aimed at the prediction of chronic toxicity [ 25 ] prompted us to apply this approach to hERG-channel blockers, a far more focused system. (springer.com)
  • It was envisaged that publicly available data on a series of hERG-channel blockers could function as a starting point for model construction, and a series of 1953 PubChem compounds could act as basis for validation. (springer.com)
  • The potassium channel gene KCNA1 was mutated to bypass post-transcriptional editing, and packaged in a non-integrating lentivector to reduce the risk of insertional mutagenesis. (ucl.ac.uk)
  • The current data support previous findings and recapitulate transcriptional regulatory alterations in genes involved in sleep, auditory function, and pain. (frontiersin.org)
  • Polymorphisms in genes of respiratory control and sudden infant death syndrome. (cdc.gov)
  • A Torkamani, N J. Schork, (2007) Distribution analysis of nonsynonymous polymorphisms within the human kinase gene family. (lu.se)
  • To study the transformative effects of oncohistone mutations in human pediatric gliomas in an otherwise isogenic context, we used CRISPR-Cas9 gene editing to revert H3.3K27M mutations in glioma cells back to wild type (WT) while in parallel introducing H3.3K27M and G34R point mutations into human astrocytes and H3.3WT glioma cells (Fig. 1a ). (nature.com)
  • The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic beta cell KATP channel) to both ATP and the sulfonylurea glibenclamide and is activated by the cardiac K(ATP) channel openers, cromakalim and pinacidil, but not by diazoxide. (nih.gov)
  • The following KCNIP1 gene cDNA ORF clone sequences were retrieved from the NCBI Reference Sequence Database (RefSeq). (genscript.com)
  • Find data in MPD that are associated with a particular mouse gene or chromosomal region. (jax.org)
  • This study was thus focused on a precise characterization of the surface residues at the face of the protein interacting with the Shaker K+ channel. (rcsb.org)