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  1 / 13467 MEDLINE  
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[PMID]:29307525
[Au] Autor:Candenas L; Pinto FM; Cejudo-Román A; González-Ravina C; Fernández-Sánchez M; Pérez-Hernández N; Irazusta J; Subirán N
[Ad] Endereço:Instituto de Investigaciones Químicas (L.C., F.M.P., A.C.-R., N.P.), CSIC, Seville, Spain. Electronic address: luzcandenas@iiq.csic.es.
[Ti] Título:Veratridine-sensitive Na channels regulate human sperm fertilization capacity.
[So] Source:Life Sci;196:48-55, 2018 Mar 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: The sperm plasma membrane contains specific ion channels and transporters that initiate changes in Ca , Na , K and H ions in the sperm cytoplasm. Ion channels are key regulators of the sperm membrane potential, cytoplasmic Ca and intracellular pH (pH ), which leads to regulate motility, capacitation, acrosome reaction and other physiological processes crucial for successful fertilization. Expression of epithelial sodium channels (ENaC) and voltage-gated sodium channels (Na ) in human spermatozoa has been reported, but the role of Na fluxes sodium channels in the regulation of sperm cell function remains poorly understood. In this context, we aimed to analyze the physiological role of Na channels in human sperm. MAIN METHODS: Motility and hyperactivation analysis was conducted by CASA analysis. Flow cytometry and spectrophotometry approaches were carried out to measure Capacitation, Acrosome reaction, immunohistochemistry for Tyr-residues phosporylation, [Ca ] levels and membrane potential. KEY FINDINGS: Functional studies showed that veratridine, a voltage-gated sodium channel activator, increased sperm progressive motility without producing hyperactivation while the Na antagonist lidocaine did induce hyperactivated motility. Veratridine increased protein tyrosine phosphorylation, an event occurring during capacitation, and its effects were inhibited in the presence of lidocaine and tetrodotoxin. Veratridine had no effect on the acrosome reaction by itself, but was able to block the progesterone-induced acrosome reaction. Moreover, veratridine caused a membrane depolarization and modified the effect of progesterone on [Ca ] and sperm membrane potential. SIGNIFICANCE: Our results suggest that veratridine-sensitive Na channels are involved on human sperm fertility acquisition regulating motility, capacitation and the progesterone-induced acrosome reaction in human sperm.
[Mh] Termos MeSH primário: Fertilização/efeitos dos fármacos
Agonistas de Canais de Sódio/farmacologia
Canais de Sódio/efeitos dos fármacos
Espermatozoides/efeitos dos fármacos
Veratridina/farmacologia
[Mh] Termos MeSH secundário: Reação Acrossômica/efeitos dos fármacos
Adolescente
Adulto
Feminino
Seres Humanos
Imuno-Histoquímica
Técnicas In Vitro
Lidocaína/farmacologia
Masculino
Potenciais da Membrana/efeitos dos fármacos
Progesterona/antagonistas & inibidores
Progesterona/farmacologia
Receptores Androgênicos/efeitos dos fármacos
Sêmen/efeitos dos fármacos
Sódio/metabolismo
Bloqueadores dos Canais de Sódio/farmacologia
Capacitação Espermática/efeitos dos fármacos
Motilidade Espermática/efeitos dos fármacos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Androgen); 0 (Sodium Channel Agonists); 0 (Sodium Channel Blockers); 0 (Sodium Channels); 4G7DS2Q64Y (Progesterone); 71-62-5 (Veratridine); 98PI200987 (Lidocaine); 9NEZ333N27 (Sodium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  2 / 13467 MEDLINE  
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[PMID]:29188980
[Au] Autor:Partanen J; Isohanni P; Auranen M
[Ti] Título:Myotonia in ion channel diseases of muscle.
[So] Source:Duodecim;132(19):1810-4, 2016.
[Is] ISSN:0012-7183
[Cp] País de publicação:Finland
[La] Idioma:eng
[Ab] Resumo:Ion channel dysfunctions of the muscular cell membrane are usually inheritable, rare diseases. They may become manifest as relatively mild symptoms of muscle stiffness and pain, myotonia or paralysis. We describe two young patients who had an inherited ion channel disease of the muscular cell membrane with mild symptoms. The first patient had a chloride channel dysfunction of the muscular cell membrane, the second one a sodium channel dysfunction. In electromyography findings typical of the respective ion channel disease were detected in both patients. Closer examination of the patients' myotonic sequences occurring in electromyography of the relaxed muscle revealed differences that already enable the evaluation of the type of ion channel disease.
[Mh] Termos MeSH primário: Canais de Cloreto/genética
Miotonia Congênita/diagnóstico
Miotonia Congênita/genética
Canais de Sódio/genética
[Mh] Termos MeSH secundário: Adolescente
Eletromiografia
Seres Humanos
Masculino
Miotonia Congênita/fisiopatologia
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chloride Channels); 0 (Sodium Channels)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


  3 / 13467 MEDLINE  
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[PMID]:28455610
[Au] Autor:Bengel P; Ahmad S; Sossalla S
[Ad] Endereço:Clinic for Cardiology and Pneumology/Heart Center, University Medical Center Goettingen, DZHK (German Centre for Cardiovascular Research), Goettingen, Germany.
[Ti] Título:Inhibition of Late Sodium Current as an Innovative Antiarrhythmic Strategy.
[So] Source:Curr Heart Fail Rep;14(3):179-186, 2017 Jun.
[Is] ISSN:1546-9549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE OF REVIEW: Over the last years, evidence is accumulating that enhanced late sodium current (I ) in cardiac pathologies has fundamental consequences for cellular electrophysiology. This review discusses the underlying mechanisms of I -induced arrhythmias and the significance of I -inhibition as a possible therapeutic approach. RECENT FINDINGS: Inhibition of enhanced I , e.g., by ranolazine, was shown to reverse these effects in different myocardial diseases including heart failure. The antianginal drug ranolazine has already been examined in larger clinical trials with promising antiarrhythmic actions. Enhanced I was found to be present in several cardiac pathologies like ischemia, long QT syndromes, hypertrophic cardiomyopathy, and heart failure. In settings of enhanced I , a sodium-dependent calcium overload leads to severe impairment of excitation-contraction coupling and therefore has a high proarrhythmogenic potential. Experimental data showed that inhibition of I has a high antiarrhythmic potential which could be confirmed in further clinical trials.
[Mh] Termos MeSH primário: Antiarrítmicos/uso terapêutico
Arritmias Cardíacas/tratamento farmacológico
Ranolazina/uso terapêutico
Bloqueadores dos Canais de Sódio/uso terapêutico
Canais de Sódio/efeitos dos fármacos
[Mh] Termos MeSH secundário: Arritmias Cardíacas/etiologia
Insuficiência Cardíaca/tratamento farmacológico
Insuficiência Cardíaca/metabolismo
Seres Humanos
Síndrome do QT Longo/metabolismo
Canais de Sódio/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Sodium Channel Blockers); 0 (Sodium Channels); A6IEZ5M406 (Ranolazine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1007/s11897-017-0333-0


  4 / 13467 MEDLINE  
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[PMID]:29216239
[Au] Autor:Van Nieuwenhuyse E; Seemann G; Panfilov AV; Vandersickel N
[Ad] Endereço:Department of Physics and Astronomy, Ghent University, Ghent, Belgium.
[Ti] Título:Effects of early afterdepolarizations on excitation patterns in an accurate model of the human ventricles.
[So] Source:PLoS One;12(12):e0188867, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Early Afterdepolarizations, EADs, are defined as the reversal of the action potential before completion of the repolarization phase, which can result in ectopic beats. However, the series of mechanisms of EADs leading to these ectopic beats and related cardiac arrhythmias are not well understood. Therefore, we aimed to investigate the influence of this single cell behavior on the whole heart level. For this study we used a modified version of the Ten Tusscher-Panfilov model of human ventricular cells (TP06) which we implemented in a 3D ventricle model including realistic fiber orientations. To increase the likelihood of EAD formation at the single cell level, we reduced the repolarization reserve (RR) by reducing the rapid delayed rectifier Potassium current and raising the L-type Calcium current. Varying these parameters defined a 2D parametric space where different excitation patterns could be classified. Depending on the initial conditions, by either exciting the ventricles with a spiral formation or burst pacing protocol, we found multiple different spatio-temporal excitation patterns. The spiral formation protocol resulted in the categorization of a stable spiral (S), a meandering spiral (MS), a spiral break-up regime (SB), spiral fibrillation type B (B), spiral fibrillation type A (A) and an oscillatory excitation type (O). The last three patterns are a 3D generalization of previously found patterns in 2D. First, the spiral fibrillation type B showed waves determined by a chaotic bi-excitable regime, i.e. mediated by both Sodium and Calcium waves at the same time and in same tissue settings. In the parameter region governed by the B pattern, single cells were able to repolarize completely and different (spiral) waves chaotically burst into each other without finishing a 360 degree rotation. Second, spiral fibrillation type A patterns consisted of multiple small rotating spirals. Single cells failed to repolarize to the resting membrane potential hence prohibiting the Sodium channel gates to recover. Accordingly, we found that Calcium waves mediated these patterns. Third, a further reduction of the RR resulted in a more exotic parameter regime whereby the individual cells behaved independently as oscillators. The patterns arose due to a phase-shift of different oscillators as disconnection of the cells resulted in continuation of the patterns. For all patterns, we computed realistic 9 lead ECGs by including a torso model. The B and A type pattern exposed the behavior of Ventricular Tachycardia (VT). We conclude that EADs at the single cell level can result in different types of cardiac fibrillation at the tissue and 3D ventricle level.
[Mh] Termos MeSH primário: Ventrículos do Coração
Modelos Biológicos
[Mh] Termos MeSH secundário: Potenciais de Ação
Canais de Cálcio Tipo L/fisiologia
Seres Humanos
Canais de Sódio/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels, L-Type); 0 (Sodium Channels)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188867


  5 / 13467 MEDLINE  
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[PMID]:29190303
[Au] Autor:Khalil S; Abbas O; Kibbi AG; Kurban M
[Ad] Endereço:Department of Dermatology, American University of Beirut, Beirut, Lebanon.
[Ti] Título:Scabies in the age of increasing drug resistance.
[So] Source:PLoS Negl Trop Dis;11(11):e0005920, 2017 Nov.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Scabies is an infestation of the skin by the mite Sarcoptes scabiei. It manifests with pruritic erythematous papules and excoriations, in addition to the pathognomonic burrows. Multiple drugs can be used for treatment, but resistance to conventional therapy is increasing throughout the years. This paper will review the mechanisms of resistance proposed in the literature and some of the potential solutions to this problem.
[Mh] Termos MeSH primário: Resistência a Inseticidas
Sarcoptes scabiei/efeitos dos fármacos
Escabiose/tratamento farmacológico
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Animais
Seres Humanos
Inseticidas/uso terapêutico
Escabiose/complicações
Escabiose/parasitologia
Pele/parasitologia
Canais de Sódio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (ATP-Binding Cassette Transporters); 0 (Insecticides); 0 (Sodium Channels)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005920


  6 / 13467 MEDLINE  
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[PMID]:28976980
[Au] Autor:McElroy T; McReynolds CN; Gulledge A; Knight KR; Smith WE; Albrecht EA
[Ad] Endereço:Department of Ecology, Evolution and Organismal Biology, Kennesaw State University, Kennesaw, GA, United States of America.
[Ti] Título:Differential toxicity and venom gland gene expression in Centruroides vittatus.
[So] Source:PLoS One;12(10):e0184695, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Variation in venom toxicity and composition exists in many species. In this study, venom potency and venom gland gene expression was evaluated in Centruroides vittatus, size class I-II (immature) and size class IV (adults/penultimate instars) size classes. Venom toxicity was evaluated by probit analysis and returned ED50 values of 50.1 µg/g for class IV compared to 134.2 µg/g for class I-II 24 hours post injection, suggesting size class IV was 2.7 fold more potent. Next generation sequencing (NGS and qPCR were used to characterize venom gland gene expression. NGS data was assembled into 36,795 contigs, and annotated using BLASTx with UNIPROT. EdgeR analysis of the sequences showed statistically significant differential expression in transcripts associated with sodium and potassium channel modulation. Sodium channel modulator expression generally favored size class IV; in contrast, potassium channel modulators were favored in size class I-II expression. Real-time quantitative PCR of 14 venom toxin transcripts detected relative expression ratios that paralleled NGS data and identified potential family members or splice variants for several sodium channel modulators. Our data suggests ontogenetic differences in venom potency and venom related genes expression exist between size classes I-II and IV.
[Mh] Termos MeSH primário: Venenos de Escorpião/toxicidade
Escorpiões/genética
[Mh] Termos MeSH secundário: Animais
DNA/genética
Sequenciamento de Nucleotídeos em Larga Escala
Canais de Potássio/efeitos dos fármacos
RNA Mensageiro/genética
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Venenos de Escorpião/genética
Escorpiões/anatomia & histologia
Canais de Sódio/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Potassium Channels); 0 (RNA, Messenger); 0 (Scorpion Venoms); 0 (Sodium Channels); 9007-49-2 (DNA)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184695


  7 / 13467 MEDLINE  
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Antunes, Edson
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[PMID]:28837636
[Au] Autor:Campos R; Mónica FZ; Rodrigues RL; Rojas-Moscoso JA; Moreno RA; Cogo JC; de Oliveira MA; Antunes E; De Nucci G
[Ad] Endereço:Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Brazil.
[Ti] Título:Tetrodotoxin-insensitive electrical field stimulation-induced contractions on Crotalus durissus terrificus corpus cavernosum.
[So] Source:PLoS One;12(8):e0183766, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reptiles are the first amniotes to develop an intromitent penis, however until now the mechanisms involved in the electrical field stimulation-induced contraction on corpora cavernosa isolated from Crotalus durissus terrificus were not investigated. Crotalus and rabbit corpora cavernosa were mounted in 10 mL organ baths for isometric tension recording. Electrical field stimulation (EFS)-induced contractions were performed in presence/absence of phentolamine (10 µM), guanethidine (30 µM), tetrodotoxin (1 µM and 1mM), A-803467 (10 µM), 3-iodo-L-Tyrosine (1 mM), salsolinol (3 µM) and a modified Krebs solution (equimolar substitution of NaCl by N-methyl-D-glucamine). Immuno-histochemistry for tyrosine hydroxylase was also performed. Electrical field stimulation (EFS; 8 Hz and 16 Hz) caused contractions in both Crotalus and rabbit corpora cavernosa. The contractions were abolished by previous incubation with either phentolamine or guanethidine. Tetrodotoxin (1 µM) also abolished the EFS-induced contractions of rabbit CC, but did not affect EFS-induced contractions of Crotalus CC. Addition of A-803467 (10 µM) did not change the EFS-induced contractions of Crotalus CC but abolished rabbit CC contractions. 3-iodo-L-Tyrosine and salsolinol had no effect on EFS-induced contractions of Crotalus CC and Rabbit CC. Replacement of NaCl by N- Methyl-D-glucamine (NMDG) abolished EFS-induced contractions of rabbit CC, but did not affect Crotalus CC. The presence of tyrosine hydroxylase was identified in endothelial cells only of Crotalus CC. Since the EFS-induced contractions of Crotalus CC is dependent on catecholamine release, insensitive to TTX, insensitive to A803467 and to NaCl replacement, it indicates that the source of cathecolamine is unlikely to be from adrenergic terminals. The finding that tyrosine hydroxylase is present in endothelial cells suggests that these cells can modulate Crotalus CC tone.
[Mh] Termos MeSH primário: Crotalus/fisiologia
Estimulação Elétrica
Pênis/efeitos dos fármacos
Tetrodotoxina/farmacologia
[Mh] Termos MeSH secundário: Compostos de Anilina/farmacologia
Animais
Callithrix
Furanos/farmacologia
Imuno-Histoquímica
Masculino
Contração Muscular/efeitos dos fármacos
Pênis/fisiologia
Coelhos
Receptores Adrenérgicos/fisiologia
Canais de Sódio/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (A 803467); 0 (Aniline Compounds); 0 (Furans); 0 (Receptors, Adrenergic); 0 (Sodium Channels); 4368-28-9 (Tetrodotoxin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183766


  8 / 13467 MEDLINE  
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[PMID]:28837624
[Au] Autor:Husser D; Ueberham L; Hindricks G; Büttner P; Ingram C; Weeke P; Shoemaker MB; Adams V; Arya A; Sommer P; Darbar D; Roden DM; Bollmann A
[Ad] Endereço:Department of Electrophysiology, University of Leipzig, Heart Center, Germany.
[Ti] Título:Rare variants in genes encoding the cardiac sodium channel and associated compounds and their impact on outcome of catheter ablation of atrial fibrillation.
[So] Source:PLoS One;12(8):e0183690, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIM: Rare variants of genes encoding the cardiac sodium channel and associated compounds have been linked with atrial fibrillation (AF). Nevertheless, current expert consensus does not support genetic testing in AF, which is in part based on the fact that "there is no therapeutic impact derived from AF genetic test results". However, there are no studies available supporting this recommendation. Consequently, this study analyzed the impact of rare variants affecting the cardiac sodium channel on rhythm outcome of AF catheter ablation. METHODS AND RESULTS: In 137 consecutive patients with lone AF enrolled in the Leipzig Heart Center AF ablation registry, screening for mutations in SCN5A, SCN1B - 4B, CAV3, GPD1L, SNTA1 and MOG1 was performed. We identified 3 rare non-synonymous variants in SCN5A, 5 in SCN1B, 1 in SCN4B, 1 in CAV3, 6 in GPD1L, 3 in SNTA1 and 3 in MOG1 (16%). Variant carriers were otherwise comparable with non-variant carriers. Analysis of AF recurrence rates after radiofrequency AF catheter ablation by serial 7-day Holter ECG monitoring between 3 and 12 months revealed no difference between groups, i.e. 45% in variant carriers vs. 49% in non-variant carriers. CONCLUSIONS: Rare variants in genes encoding the cardiac sodium channel and associated compounds are frequently found in lone AF but were not found to impact the outcome of AF catheter ablation. This finding supports current recommendations not to screen for rare variants for the ablation outcome in AF. Nevertheless, it may at least be helpful for understanding AF mechanisms and larger studies are needed to further explore the possible association between genotype and response to AF therapies.
[Mh] Termos MeSH primário: Fibrilação Atrial/cirurgia
Ablação por Cateter/métodos
Miocárdio/metabolismo
Canais de Sódio/genética
[Mh] Termos MeSH secundário: Seres Humanos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sodium Channels)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183690


  9 / 13467 MEDLINE  
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[PMID]:28833464
[Au] Autor:Hawash AA; Voss AA; Rich MM
[Ad] Endereço:Department of Neuroscience, Cell Biology, and Physiology, Wright State University, Dayton, OH.
[Ti] Título:Inhibiting persistent inward sodium currents prevents myotonia.
[So] Source:Ann Neurol;82(3):385-395, 2017 Sep.
[Is] ISSN:1531-8249
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the ClC-1 chloride channel in skeletal muscle, which causes involuntary firing of muscle action potentials (myotonia), producing muscle stiffness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. Our goal was to identify currents that trigger spontaneous firing of muscle in the setting of reduced ClC-1 current. METHODS: In vitro intracellular current clamp and voltage clamp recordings were performed in muscle from a mouse model of myotonia congenita. RESULTS: Intracellular recordings revealed a slow afterdepolarization (AfD) that triggers myotonic action potentials. The AfD is well explained by a tetrodotoxin-sensitive and voltage-dependent Na persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, suggesting this may contribute to the end of myotonic runs. Highlighting the significance of this mechanism, we found that ranolazine and elevated serum divalent cations eliminate myotonia by inhibiting AfD and NaPIC. INTERPRETATION: This work significantly changes our understanding of the mechanisms triggering myotonia. Our work suggests that the current focus of treating myotonia, blocking the transient Na current underlying action potentials, is an inefficient approach. We show that inhibiting NaPIC is paralleled by elimination of myotonia. We suggest the ideal myotonia therapy would selectively block NaPIC and spare the transient Na current. Ann Neurol 2017;82:385-395.
[Mh] Termos MeSH primário: Potenciais de Ação/fisiologia
Músculo Esquelético/fisiopatologia
Miotonia Congênita/fisiopatologia
Canais de Sódio/fisiologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Camundongos
Contração Muscular/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sodium Channels)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1002/ana.25017


  10 / 13467 MEDLINE  
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[PMID]:28739252
[Au] Autor:Szulczyk B; Nurowska E
[Ad] Endereço:Department of Drug Technology and Pharmaceutical Biotechnology, The Medical University of Warsaw, Banacha 1, 02-097, Poland. Electronic address: bartlomiej.szulczyk@wum.edu.pl.
[Ti] Título:Valproic acid inhibits TTX-resistant sodium currents in prefrontal cortex pyramidal neurons.
[So] Source:Biochem Biophys Res Commun;491(2):291-295, 2017 Sep 16.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Valproic acid is frequently prescribed and used to treat epilepsy, bipolar disorder and other conditions. However, the mechanism of action of valproic acid has not been fully elucidated. The aim of this study was to assess the influence of valproic acid (200 µM) on TTX-resistant sodium currents in mPFC pyramidal neurons. Valproic acid inhibited the maximal amplitude and did not change the activation parameters of TTX-resistant sodium currents. Moreover, valproic acid (2 µM and 200 µM) shifted the TTX-resistant sodium channel inactivation curve towards hyperpolarisation. In the presence of valproic acid, TTX-resistant sodium currents recovered from inactivation more slowly. Valproic acid did not influence the use-dependent blockade of TTX-resistant sodium currents. This study suggests that a potential new mechanism of the antiepileptic action of valproic acid is, among others, inhibition of TTX-resistant sodium currents.
[Mh] Termos MeSH primário: Anticonvulsivantes/farmacologia
Células Piramidais/efeitos dos fármacos
Bloqueadores dos Canais de Sódio/farmacologia
Canais de Sódio/metabolismo
Tetrodotoxina/farmacologia
Ácido Valproico/farmacologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Potenciais de Ação/fisiologia
Animais
Técnicas de Cultura de Células
Microtomia
Técnicas de Patch-Clamp
Córtex Pré-Frontal/citologia
Córtex Pré-Frontal/efeitos dos fármacos
Córtex Pré-Frontal/metabolismo
Cultura Primária de Células
Células Piramidais/citologia
Células Piramidais/metabolismo
Ratos
Sódio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Sodium Channel Blockers); 0 (Sodium Channels); 4368-28-9 (Tetrodotoxin); 614OI1Z5WI (Valproic Acid); 9NEZ333N27 (Sodium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE



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