Base de dados : MEDLINE
Pesquisa : D12.776.157.530.400.875.750.300 [Categoria DeCS]
Referências encontradas : 107 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 11 ir para página                         

  1 / 107 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28683073
[Au] Autor:Li T; Lu G; Chiang EY; Chernov-Rogan T; Grogan JL; Chen J
[Ad] Endereço:Department of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, California, United States of America.
[Ti] Título:High-throughput electrophysiological assays for voltage gated ion channels using SyncroPatch 768PE.
[So] Source:PLoS One;12(7):e0180154, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ion channels regulate a variety of physiological processes and represent an important class of drug target. Among the many methods of studying ion channel function, patch clamp electrophysiology is considered the gold standard by providing the ultimate precision and flexibility. However, its utility in ion channel drug discovery is impeded by low throughput. Additionally, characterization of endogenous ion channels in primary cells remains technical challenging. In recent years, many automated patch clamp (APC) platforms have been developed to overcome these challenges, albeit with varying throughput, data quality and success rate. In this study, we utilized SyncroPatch 768PE, one of the latest generation APC platforms which conducts parallel recording from two-384 modules with giga-seal data quality, to push these 2 boundaries. By optimizing various cell patching parameters and a two-step voltage protocol, we developed a high throughput APC assay for the voltage-gated sodium channel Nav1.7. By testing a group of Nav1.7 reference compounds' IC50, this assay was proved to be highly consistent with manual patch clamp (R > 0.9). In a pilot screening of 10,000 compounds, the success rate, defined by > 500 MΩ seal resistance and >500 pA peak current, was 79%. The assay was robust with daily throughput ~ 6,000 data points and Z' factor 0.72. Using the same platform, we also successfully recorded endogenous voltage-gated potassium channel Kv1.3 in primary T cells. Together, our data suggest that SyncroPatch 768PE provides a powerful platform for ion channel research and drug discovery.
[Mh] Termos MeSH primário: Ensaios de Triagem em Larga Escala/métodos
Potenciais da Membrana/fisiologia
Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo
Técnicas de Patch-Clamp/métodos
Bloqueadores dos Canais de Potássio/farmacologia
Bloqueadores dos Canais de Sódio/farmacologia
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetulus
Avaliação Pré-Clínica de Medicamentos
Expressão Gênica
Ensaios de Triagem em Larga Escala/instrumentação
Canal de Potássio Kv1.3/deficiência
Canal de Potássio Kv1.3/genética
Canal de Sódio Disparado por Voltagem NAV1.1/genética
Canal de Sódio Disparado por Voltagem NAV1.1/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.2/genética
Canal de Sódio Disparado por Voltagem NAV1.2/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.3/genética
Canal de Sódio Disparado por Voltagem NAV1.3/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.4/genética
Canal de Sódio Disparado por Voltagem NAV1.4/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.5/genética
Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.6/genética
Canal de Sódio Disparado por Voltagem NAV1.6/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.7/genética
Técnicas de Patch-Clamp/instrumentação
Cultura Primária de Células
Ratos
Canais de Sódio/genética
Canais de Sódio/metabolismo
Linfócitos T/citologia
Linfócitos T/efeitos dos fármacos
Linfócitos T/metabolismo
Transgenes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Kv1.3 Potassium Channel); 0 (NAV1.1 Voltage-Gated Sodium Channel); 0 (NAV1.2 Voltage-Gated Sodium Channel); 0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (NAV1.4 Voltage-Gated Sodium Channel); 0 (NAV1.5 Voltage-Gated Sodium Channel); 0 (NAV1.6 Voltage-Gated Sodium Channel); 0 (NAV1.7 Voltage-Gated Sodium Channel); 0 (Potassium Channel Blockers); 0 (SCN1A protein, human); 0 (SCN3A protein, human); 0 (SCN4A protein, human); 0 (SCN5A protein, human); 0 (SCN8A protein, human); 0 (SCN9A protein, human); 0 (Sodium Channel Blockers); 0 (Sodium Channels)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180154


  2 / 107 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27848944
[Au] Autor:Trujillano D; Bertoli-Avella AM; Kumar Kandaswamy K; Weiss ME; Köster J; Marais A; Paknia O; Schröder R; Garcia-Aznar JM; Werber M; Brandau O; Calvo Del Castillo M; Baldi C; Wessel K; Kishore S; Nahavandi N; Eyaid W; Al Rifai MT; Al-Rumayyan A; Al-Twaijri W; Alothaim A; Alhashem A; Al-Sannaa N; Al-Balwi M; Alfadhel M; Rolfs A; Abou Jamra R
[Ad] Endereço:Centogene AG, Rostock, Germany.
[Ti] Título:Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
[So] Source:Eur J Hum Genet;25(2):176-182, 2017 Feb.
[Is] ISSN:1476-5438
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We report our results of 1000 diagnostic WES cases based on 2819 sequenced samples from 54 countries with a wide phenotypic spectrum. Clinical information given by the requesting physicians was translated to HPO terms. WES processes were performed according to standardized settings. We identified the underlying pathogenic or likely pathogenic variants in 307 families (30.7%). In further 253 families (25.3%) a variant of unknown significance, possibly explaining the clinical symptoms of the index patient was identified. WES enabled timely diagnosing of genetic diseases, validation of causality of specific genetic disorders of PTPN23, KCTD3, SCN3A, PPOX, FRMPD4, and SCN1B, and setting dual diagnoses by detecting two causative variants in distinct genes in the same patient. We observed a better diagnostic yield in consanguineous families, in severe and in syndromic phenotypes. Our results suggest that WES has a better yield in patients that present with several symptoms, rather than an isolated abnormality. We also validate the clinical benefit of WES as an effective diagnostic tool, particularly in nonspecific or heterogeneous phenotypes. We recommend WES as a first-line diagnostic in all cases without a clear differential diagnosis, to facilitate personal medical care.
[Mh] Termos MeSH primário: Exoma
Testes Genéticos/métodos
Técnicas de Genotipagem/métodos
Análise de Sequência de DNA/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Pré-Escolar
Feminino
Flavoproteínas/genética
Testes Genéticos/normas
Técnicas de Genotipagem/normas
Seres Humanos
Lactente
Recém-Nascido
Peptídeos e Proteínas de Sinalização Intracelular/genética
Masculino
Meia-Idade
Proteínas Mitocondriais/genética
Canal de Sódio Disparado por Voltagem NAV1.3/genética
Núcleo Familiar
Fenótipo
Canais de Potássio/genética
Proteínas Tirosina Fosfatases não Receptoras/genética
Protoporfirinogênio Oxidase/genética
Análise de Sequência de DNA/normas
Canais de Sódio/genética
Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Flavoproteins); 0 (Intracellular Signaling Peptides and Proteins); 0 (KCTD3 protein, human); 0 (Mitochondrial Proteins); 0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (Potassium Channels); 0 (Preso protein, human); 0 (SCN1B protein, human); 0 (SCN3A protein, human); 0 (Sodium Channels); 0 (Voltage-Gated Sodium Channel beta-1 Subunit); EC 1.3.3.4 (PPOX protein, human); EC 1.3.3.4 (Protoporphyrinogen Oxidase); EC 3.1.3.48 (PTPN23 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170705
[Lr] Data última revisão:
170705
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161117
[St] Status:MEDLINE
[do] DOI:10.1038/ejhg.2016.146


  3 / 107 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27816501
[Au] Autor:Lin GW; Lu P; Zeng T; Tang HL; Chen YH; Liu SJ; Gao MM; Zhao QH; Yi YH; Long YS
[Ad] Endereço:Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou 501260, China.
[Ti] Título:GAPDH-mediated posttranscriptional regulations of sodium channel Scn1a and Scn3a genes under seizure and ketogenic diet conditions.
[So] Source:Neuropharmacology;113(Pt A):480-489, 2017 Feb.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Abnormal expressions of sodium channel SCN1A and SCN3A genes alter neural excitability that are believed to contribute to the pathogenesis of epilepsy, a long-term risk of recurrent seizures. Ketogenic diet (KD), a high-fat and low-carbohydrate treatment for difficult-to-control (refractory) epilepsy in children, has been suggested to reverse gene expression patterns. Here, we reveal a novel role of GAPDH on the posttranscriptional regulation of mouse Scn1a and Scn3a expressions under seizure and KD conditions. We show that GAPDH binds to a conserved region in the 3' UTRs of human and mouse SCN1A and SCN3A genes, which decreases and increases genes' expressions by affecting mRNA stability through SCN1A 3' UTR and SCN3A 3' UTR, respectively. In seizure mice, the upregulation and phosphorylation of GAPDH enhance its binding to the 3' UTR, which lead to downregulation of Scn1a and upregulation of Scn3a. Furthermore, administration of KD generates ß-hydroxybutyric acid which rescues the abnormal expressions of Scn1a and Scn3a by weakening the GAPDH's binding to the element. Taken together, these data suggest that GAPDH-mediated expression regulation of sodium channel genes may be associated with epilepsy and the anticonvulsant action of KD.
[Mh] Termos MeSH primário: Dieta Cetogênica
Gliceraldeído-3-Fosfato Desidrogenases/fisiologia
Canal de Sódio Disparado por Voltagem NAV1.1/genética
Canal de Sódio Disparado por Voltagem NAV1.3/genética
Convulsões/dietoterapia
Convulsões/genética
Canais de Sódio/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Dieta Cetogênica/métodos
Células HEK293
Seres Humanos
Masculino
Camundongos
Canal de Sódio Disparado por Voltagem NAV1.1/biossíntese
Canal de Sódio Disparado por Voltagem NAV1.3/biossíntese
Ligação Proteica/fisiologia
Processamento Pós-Transcricional do RNA/fisiologia
Convulsões/metabolismo
Canais de Sódio/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NAV1.1 Voltage-Gated Sodium Channel); 0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (SCN1A protein, human); 0 (SCN3A protein, human); 0 (Sodium Channels); EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE


  4 / 107 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27153334
[Au] Autor:Thuresson AC; Van Buggenhout G; Sheth F; Kamate M; Andrieux J; Clayton Smith J; Soussi Zander C
[Ad] Endereço:Department of Immunology, Genetics and Pathology, Rudbeck and Science for Life laboratory, Uppsala University, Uppsala, Sweden.
[Ti] Título:Whole gene duplication of SCN2A and SCN3A is associated with neonatal seizures and a normal intellectual development.
[So] Source:Clin Genet;91(1):106-110, 2017 Jan.
[Is] ISSN:1399-0004
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:Duplications at 2q24.3 encompassing the voltage-gated sodium channel gene cluster are associated with early onset epilepsy. All cases described in the literature have presented in addition with different degrees of intellectual disability, and have involved neighbouring genes in addition to the sodium channel gene cluster. Here, we report eight new cases with overlapping duplications at 2q24 ranging from 0.05 to 7.63 Mb in size. Taken together with the previously reported cases, our study suggests that having an extra copy of SCN2A has an effect on epilepsy pathogenesis, causing benign familial infantile seizures which eventually disappear at the age of 1-2 years. However, the number of copies of SCN2A does not appear to have an effect on cognitive outcome.
[Mh] Termos MeSH primário: Duplicação Gênica
Predisposição Genética para Doença/genética
Canal de Sódio Disparado por Voltagem NAV1.2/genética
Canal de Sódio Disparado por Voltagem NAV1.3/genética
Convulsões/genética
Canais de Sódio/genética
[Mh] Termos MeSH secundário: Adolescente
Idade de Início
Criança
Desenvolvimento Infantil
Pré-Escolar
Cromossomos Humanos Par 2/genética
Feminino
Seres Humanos
Hibridização in Situ Fluorescente
Recém-Nascido
Inteligência
Masculino
Convulsões/psicologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NAV1.2 Voltage-Gated Sodium Channel); 0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (SCN2A protein, human); 0 (SCN3A protein, human); 0 (Sodium Channels)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160507
[St] Status:MEDLINE
[do] DOI:10.1111/cge.12797


  5 / 107 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27013471
[Au] Autor:Tan NN; Tang HL; Lin GW; Chen YH; Lu P; Li HJ; Gao MM; Zhao QH; Yi YH; Liao WP; Long YS
[Ad] Endereço:Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, 250 Changang East Road, Guangzhou, 510260, China.
[Ti] Título:Epigenetic Downregulation of Scn3a Expression by Valproate: a Possible Role in Its Anticonvulsant Activity.
[So] Source:Mol Neurobiol;54(4):2831-2842, 2017 05.
[Is] ISSN:1559-1182
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Upregulation of sodium channel SCN3A expression in epileptic tissues is known to contribute to enhancing neuronal excitability and the development of epilepsy. Therefore, certain strategies to reduce SCN3A expression may be helpful for seizure control. Here, we reveal a novel role of valproate (VPA) in the epigenetic downregulation of Scn3a expression. We found that VPA, instead of carbamazepine (CBZ) and lamotrigine (LTG), could significantly downregulate Scn3a expression in mouse Neuro-2a cells. Luciferase assays and CpG methylation analyses showed that VPA induced the methylation at the -39C site in Scn3a promoter which decreased the promoter activity. We further showed that VPA downregulated the expression of methyl-CpG-binding domain protein 2 (MBD2) at the posttranscriptional level and knockdown of MBD2 increased Scn3a expression. In addition, we found that VPA induced the expression of fat mass and obesity-associated (FTO) protein and FTO knockdown abolished the repressive effects of VPA on MBD2 and Na 1.3 expressions. Furthermore, VPA, instead of other two anticonvulsant drugs, induced the expressions of Scn3a and Mbd2 and reduced Fto expression in the hippocampus of VPA-treated seizure mice. Taken together, this study suggests an epigenetic pathway for the VPA-induced downregulation of Scn3a expression, which provides a possible role of this pathway in the anticonvulsant action of VPA.
[Mh] Termos MeSH primário: Anticonvulsivantes/farmacologia
Regulação para Baixo/genética
Epigênese Genética/efeitos dos fármacos
Canal de Sódio Disparado por Voltagem NAV1.3/genética
Ácido Valproico/farmacologia
[Mh] Termos MeSH secundário: Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética
Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo
Animais
Anticonvulsivantes/uso terapêutico
Linhagem Celular Tumoral
Ilhas de CpG/genética
Metilação de DNA/efeitos dos fármacos
Metilação de DNA/genética
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Regulação para Baixo/efeitos dos fármacos
Genes Reporter
Hipocampo/metabolismo
Masculino
Camundongos
Modelos Biológicos
Canal de Sódio Disparado por Voltagem NAV1.3/metabolismo
Regiões Promotoras Genéticas
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Convulsões/tratamento farmacológico
Convulsões/genética
Transcrição Genética/efeitos dos fármacos
Ácido Valproico/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (DNA-Binding Proteins); 0 (Mbd2 protein, mouse); 0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (RNA, Messenger); 0 (Scn3a protein, mouse); 614OI1Z5WI (Valproic Acid); EC 1.14.11.- (FTO protein, mouse); EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160326
[St] Status:MEDLINE
[do] DOI:10.1007/s12035-016-9871-9


  6 / 107 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27608006
[Au] Autor:Yang L; Li Q; Liu X; Liu S
[Ad] Endereço:Department of Endocrinology, The General Hospital of the PLA Rocket Force, Beijing 100088, China. ylynn1028@126.com.
[Ti] Título:Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy.
[So] Source:Int J Mol Sci;17(9), 2016 Sep 05.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause-effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.
[Mh] Termos MeSH primário: Diabetes Mellitus/metabolismo
Neuropatias Diabéticas/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.3/metabolismo
Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Ilhotas Pancreáticas/metabolismo
Bloqueadores dos Canais de Sódio/farmacologia
Tetrodotoxina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (NAV1.7 Voltage-Gated Sodium Channel); 0 (Sodium Channel Blockers); 4368-28-9 (Tetrodotoxin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170323
[Lr] Data última revisão:
170323
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160909
[St] Status:MEDLINE


  7 / 107 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27072680
[Au] Autor:Kubat Öktem E; Mruk K; Chang J; Akin A; Kobertz WR; Brown RH
[Ad] Endereço:Institute of Biomedical Engineering, Bogaziçi University, Istanbul, Turkey. kubatelif@gmail.com.
[Ti] Título:Mutant SOD1 protein increases Nav1.3 channel excitability.
[So] Source:J Biol Phys;42(3):351-70, 2016 06.
[Is] ISSN:1573-0689
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Amyotrophic lateral sclerosis (ALS) is a lethal paralytic disease caused by the degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) are present in ~20% of familial ALS and ~2% of all ALS cases. The most common SOD1 gene mutation in North America is a missense mutation substituting valine for alanine (A4V). In this study, we analyze sodium channel currents in oocytes expressing either wild-type or mutant (A4V) SOD1 protein. We demonstrate that the A4V mutation confers a propensity to hyperexcitability on a voltage-dependent sodium channel (Nav1.3) mediated by heightened total Na(+) conductance and a hyperpolarizing shift in the voltage dependence of Nav1.3 activation. To estimate the impact of these channel effects on excitability in an intact neuron, we simulated these changes in the program NEURON; this shows that the changes induced by mutant SOD1 increase the spontaneous firing frequency of the simulated neuron. These findings are consistent with the view that excessive excitability of neurons is one component in the pathogenesis of this disease.
[Mh] Termos MeSH primário: Fenômenos Eletrofisiológicos/genética
Mutação
Canal de Sódio Disparado por Voltagem NAV1.3/metabolismo
Superóxido Dismutase-1/genética
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Neurônios/citologia
Sódio/metabolismo
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (NAV1.3 Voltage-Gated Sodium Channel); 9NEZ333N27 (Sodium); EC 1.15.1.1 (Superoxide Dismutase-1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171112
[Lr] Data última revisão:
171112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160414
[St] Status:MEDLINE
[do] DOI:10.1007/s10867-016-9411-x


  8 / 107 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26729167
[Au] Autor:Wang G; Rong MQ; Li Q; Liu YP; Long CB; Meng P; Yao HM; Lai R; Luo XD
[Ad] Endereço:College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. wang.gan@outlook.com.
[Ti] Título:Alkaloids from Veratrum taliense Exert Cardiovascular Toxic Effects via Cardiac Sodium Channel Subtype 1.5.
[So] Source:Toxins (Basel);8(1), 2015 Dec 30.
[Is] ISSN:2072-6651
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Several species of the genus Veratrum that produce steroid alkaloids are commonly used to treat pain and hypertension in China and Europe. However, Veratrum alkaloids (VAs) induce serious cardiovascular toxicity. In China, Veratrum treatment often leads to many side effects and even causes the death of patients, but the pathophysiological mechanisms under these adverse effects are not clear. Here, two solanidine-type VAs (isorubijervine and rubijervine) isolated from Veratrum taliense exhibited strong cardiovascular toxicity. A pathophysiological study indicated that these VAs blocked sodium channels Na(V)1.3-1.5 and exhibited the strongest ability to inhibit Na(V)1.5, which is specifically expressed in cardiac tissue and plays an essential role in cardiac physiological function. This result reveals that VAs exert their cardiovascular toxicity via the Na(V)1.5 channel. The effects of VAs on Na(V)1.3 and Na(V)1.4 may be related to their analgesic effect and skeletal muscle toxicity, respectively.
[Mh] Termos MeSH primário: Alcaloides/toxicidade
Coração/efeitos dos fármacos
Canal de Sódio Disparado por Voltagem NAV1.5/fisiologia
Veratrum
[Mh] Termos MeSH secundário: Animais
Pressão Sanguínea/efeitos dos fármacos
Eletrocardiografia
Coração/fisiologia
Frequência Cardíaca/efeitos dos fármacos
Seres Humanos
Dose Letal Mediana
Macaca
Masculino
Camundongos
Canal de Sódio Disparado por Voltagem NAV1.3/fisiologia
Canal de Sódio Disparado por Voltagem NAV1.4/fisiologia
Raízes de Plantas
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (NAV1.4 Voltage-Gated Sodium Channel); 0 (NAV1.5 Voltage-Gated Sodium Channel); 0 (SCN5A protein, human)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160106
[St] Status:MEDLINE


  9 / 107 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26220736
[Au] Autor:Wang L; Zellmer SG; Printzenhoff DM; Castle NA
[Ad] Endereço:Glaxo SmithKline, Shanghai, China.
[Ti] Título:Addition of a single methyl group to a small molecule sodium channel inhibitor introduces a new mode of gating modulation.
[So] Source:Br J Pharmacol;172(20):4905-18, 2015 Oct.
[Is] ISSN:1476-5381
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Aryl sulfonamide Nav 1.3 or Nav 1.7 voltage-gated sodium (Nav ) channel inhibitors interact with the Domain 4 voltage sensor domain (D4 VSD). During studies to better understand the structure-activity relationship of this interaction, an additional mode of channel modulation, specifically slowing of inactivation, was revealed by addition of a single methyl moiety. The objective of the current study was to determine if these different modulatory effects are mediated by the same or distinct interactions with the channel. EXPERIMENTAL APPROACH: Electrophysiology and site-directed mutation were used to compare the effects of PF-06526290 and its desmethyl analogue PF-05661014 on Nav channel function. KEY RESULTS: PF-05661014 selectively inhibits Nav 1.3 versus Nav 1.7 currents by stabilizing inactivated channels via interaction with D4 VSD. In contrast, PF-06526290, which differs from PF-05661014 by a single methyl group, exhibits a dual effect. It greatly slows inactivation of Nav channels in a subtype-independent manner. However, upon prolonged depolarization to induce inactivation, PF-06526290 becomes a Nav subtype selective inhibitor similar to PF-05661014. Mutation of the D4 VSD modulates inhibition of Nav 1.3 or Nav 1.7 by both PF-05661014 and PF-06526290, but has no effect on the inactivation slowing produced by PF-06526290. This finding, along with the absence of functional inhibition of PF-06526290-induced inactivation slowing by PF-05661014, suggests that distinct interactions underlie the two modes of Nav channel modulation. CONCLUSIONS AND IMPLICATIONS: Addition of a methyl group to a Nav channel inhibitor introduces an additional mode of gating modulation, implying that a single compound can affect sodium channel function in multiple ways.
[Mh] Termos MeSH primário: Canal de Sódio Disparado por Voltagem NAV1.3/fisiologia
Canal de Sódio Disparado por Voltagem NAV1.7/fisiologia
Bloqueadores dos Canais de Sódio/farmacologia
Canais de Sódio/fisiologia
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Animais
Células CHO
Cricetulus
Gânglios Espinais/efeitos dos fármacos
Gânglios Espinais/fisiologia
Células HEK293
Seres Humanos
Ativação do Canal Iônico/efeitos dos fármacos
Metilação
Camundongos
Mutagênese Sítio-Dirigida
Canal de Sódio Disparado por Voltagem NAV1.3/genética
Canal de Sódio Disparado por Voltagem NAV1.7/genética
Células Receptoras Sensoriais/efeitos dos fármacos
Células Receptoras Sensoriais/fisiologia
Bloqueadores dos Canais de Sódio/química
Canais de Sódio/genética
Relação Estrutura-Atividade
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (NAV1.7 Voltage-Gated Sodium Channel); 0 (SCN3A protein, human); 0 (SCN9A protein, human); 0 (Sodium Channel Blockers); 0 (Sodium Channels); 0 (Sulfonamides)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170412
[Lr] Data última revisão:
170412
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150730
[St] Status:MEDLINE
[do] DOI:10.1111/bph.13259


  10 / 107 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26156380
[Au] Autor:Estacion M; Vohra BP; Liu S; Hoeijmakers J; Faber CG; Merkies IS; Lauria G; Black JA; Waxman SG
[Ad] Endereço:Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; Center for Neuroscience and Regeneration Research, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut;
[Ti] Título:Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation.
[So] Source:J Neurophysiol;114(3):1554-64, 2015 Sep.
[Is] ISSN:1522-1598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gain-of-function missense mutations in voltage-gated sodium channel Nav1.7 have been linked to small-fiber neuropathy, which is characterized by burning pain, dysautonomia and a loss of intraepidermal nerve fibers. However, the mechanistic cascades linking Nav1.7 mutations to axonal degeneration are incompletely understood. The G856D mutation in Nav1.7 produces robust changes in channel biophysical properties, including hyperpolarized activation, depolarized inactivation, and enhanced ramp and persistent currents, which contribute to the hyperexcitability exhibited by neurons containing Nav1.8. We report here that cell bodies and neurites of dorsal root ganglion (DRG) neurons transfected with G856D display increased levels of intracellular Na(+) concentration ([Na(+)]) and intracellular [Ca(2+)] following stimulation with high [K(+)] compared with wild-type (WT) Nav1.7-expressing neurons. Blockade of reverse mode of the sodium/calcium exchanger (NCX) or of sodium channels attenuates [Ca(2+)] transients evoked by high [K(+)] in G856D-expressing DRG cell bodies and neurites. We also show that treatment of WT or G856D-expressing neurites with high [K(+)] or 2-deoxyglucose (2-DG) does not elicit degeneration of these neurites, but that high [K(+)] and 2-DG in combination evokes degeneration of G856D neurites but not WT neurites. Our results also demonstrate that 0 Ca(2+) or blockade of reverse mode of NCX protects G856D-expressing neurites from degeneration when exposed to high [K(+)] and 2-DG. These results point to [Na(+)] overload in DRG neurons expressing mutant G856D Nav1.7, which triggers reverse mode of NCX and contributes to Ca(2+) toxicity, and suggest subtype-specific blockade of Nav1.7 or inhibition of reverse NCX as strategies that might slow or prevent axon degeneration in small-fiber neuropathy.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Eritromelalgia/metabolismo
Gânglios Espinais/metabolismo
Mutação de Sentido Incorreto
Canal de Sódio Disparado por Voltagem NAV1.3/metabolismo
Neuritos/metabolismo
Canais de Sódio/metabolismo
Trocador de Sódio e Cálcio/metabolismo
[Mh] Termos MeSH secundário: Animais
Cálcio/toxicidade
Células Cultivadas
Gânglios Espinais/citologia
Seres Humanos
Canal de Sódio Disparado por Voltagem NAV1.3/genética
Neuritos/patologia
Potássio/metabolismo
Ratos
Ratos Sprague-Dawley
Sódio/metabolismo
Canais de Sódio/genética
Trocador de Sódio e Cálcio/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (NAV1.3 Voltage-Gated Sodium Channel); 0 (SCN3A protein, human); 0 (Sodium Channels); 0 (Sodium-Calcium Exchanger); 9NEZ333N27 (Sodium); RWP5GA015D (Potassium); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161025
[Lr] Data última revisão:
161025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150710
[St] Status:MEDLINE
[do] DOI:10.1152/jn.00195.2015



página 1 de 11 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde