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1.
Artigo em Espanhol | LILACS, CUMED | ID: lil-773357

RESUMO

En la búsqueda de nuevas opciones terapéuticas para el tratamiento del dolor, se ha llegado al descubrimiento de canales iónicos que actúan como receptores y están presentes en neuronas nociceptoras aferentes primarias. Entre estos receptores, se encuentran los canales iónicos receptores de potencial transitorio que regulan las vías involucradas en el dolor y la nocicepción. Se realizó una revisión actualizada de los principales canales iónicos receptores de potencial transitorio implicados en la fisiopatología del dolor. Se hace una reseña histórica del descubrimiento de estas moléculas y sus estudios avanzados. A continuación se revisan las diferentes familias de estos canales con su clasificación, nomenclatura, estructura y funciones celulares. También se hace un recuento de la relación de estos canales con la analgesia, así como el mecanismo de acción de algunos analgésicos que actúan sobre ellos. Finalmente, se detallan importantes consideraciones a tomar en cuenta, que pudieran influir sobre la utilización de estos medicamentos en la clínica. Por tal motivo, el trabajo procura ser una revisión que abarque el rol de los canales TRP como nuevas dianas farmacológicas en el tratamiento del dolor.


In the search for new therapeutic options for pain treatment, new ion channels have been discovered, which act as receptors and are present in primary afferent nociceptor neurons. Some of them are the transient receptor potential ion channels that regulate the pathways involved in pain and nociception. An updated review of the main transient potential receptors ion channels involved in pain physiopathology and a historical review of the discovery of these molecules and advanced studies on them were also made. Then the different families of these channels with their classification, nomenclature, structure and cell functions were also examined. An account of the relationships of these channels with analgesia as well as the mechanism of action of some analgesics acting upon them was also presented. Finally, important considerations were given, which should be taken into account since they might influence on the clinical use of these drugs. For these reasons, the paper intends to be a review covering the role of the transient receptor potential channels as new pharmacological targets in the pain treatment.


Assuntos
Humanos , Capsaicina/uso terapêutico , Ativação do Canal Iônico/efeitos dos fármacos , Manejo da Dor/métodos , Analgésicos/uso terapêutico
2.
Dental press j. orthod. (Impr.) ; 20(3): 109-117, May-Jun/2015. graf
Artigo em Inglês | LILACS | ID: lil-751407

RESUMO

INTRODUCTION: The indirect bonding technique optimizes fixed appliance installation at the orthodontic office, ensuring precise bracket positioning, among other advantages. In this laboratory clinical phase, material and methods employed in creating the transfer tray are decisive to accuracy. OBJECTIVE: This article describes a simple, efficient and reproducible indirect bonding technique that allows the procedure to be carried out successfully. Variables influencing the orthodontic bonding are analyzed and discussed in order to aid professionals wishing to adopt the indirect bonding technique routinely in their clinical practice. .


INTRODUÇÃO: a técnica de colagem indireta prioriza a otimização do procedimento de montagem do aparelho fixo na clínica ortodôntica, assegurando, entre outras, vantagens relacionadas à precisão no posicionamento dos braquetes. Nesse procedimento clínico laboratorial, o material e o método de confecção da moldeira de transferência são determinantes no quesito precisão. OBJETIVO: este artigo descreve uma técnica de colagem indireta simples, eficiente e reprodutível, para que o procedimento possa ser realizado com sucesso. Variáveis que exercem influência sobre o procedimento são analisadas e discutidas, a fim de auxiliar o profissional a adotar, de forma rotineira, a técnica de colagem indireta em sua prática clínica. .


Assuntos
Humanos , Canais Iônicos/metabolismo , Técnicas de Patch-Clamp/métodos , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Ativação do Canal Iônico , Canais Iônicos/química , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismo
3.
Radiol. bras ; 48(2): 86-92, Mar-Apr/2015. tab
Artigo em Inglês | LILACS | ID: lil-746624

RESUMO

Objective: To evaluate the evolution of mammographic image quality in the state of Rio de Janeiro on the basis of parameters measured and analyzed during health surveillance inspections in the period from 2006 to 2011. Materials and Methods: Descriptive study analyzing parameters connected with imaging quality of 52 mammography apparatuses inspected at least twice with a one-year interval. Results: Amongst the 16 analyzed parameters, 7 presented more than 70% of conformity, namely: compression paddle pressure intensity (85.1%), films development (72.7%), film response (72.7%), low contrast fine detail (92.2%), tumor mass visualization (76.5%), absence of image artifacts (94.1%), mammography-specific developers availability (88.2%). On the other hand, relevant parameters were below 50% conformity, namely: monthly image quality control testing (28.8%) and high contrast details with respect to microcalcifications visualization (47.1%). Conclusion: The analysis revealed critical situations in terms of compliance with the health surveillance standards. Priority should be given to those mammography apparatuses that remained non-compliant at the second inspection performed within the one-year interval. .


Objetivo: Avaliar a evolução da qualidade da imagem de mamógrafos localizados no Estado do Rio de Janeiro, de 2006 a 2011, com base em parâmetros medidos e observados durante inspeções sanitárias. Materiais e Métodos: Estudo descritivo sobre a evolução de parâmetros que condicionam a qualidade da imagem focalizou 52 mamógrafos, inspecionados no mínimo duas vezes, com intervalo de um ano. Resultados: Dos 16 parâmetros avaliados, 7 apresentaram mais de 70% de conformidade: força do dispositivo de compressão (85,1%), processamento dos filmes (72,7%), resposta do filme do serviço (72,7%), detalhes lineares de baixo contraste (92,2%), visualização de massas tumorais (76,5%), ausência de artefatos de imagem (94,1%), existência de processadoras específicas para mamografia (88,2%). Importantes parâmetros apresentaram-se abaixo de 50% de conformidade: realização de testes mensais da qualidade de imagem pelo estabelecimento (28,8%) e detalhes de alto contraste, que dizem respeito à visualização de microcalcificações (47,1%). Conclusão: A análise revelou situações críticas da atuação da vigilância sanitária, cuja prioridade deveria ser dirigida aos estacionários, ou seja, os mamógrafos que permaneceram na situação de não conformidade nas inspeções realizadas com intervalo de um ano. .


Assuntos
Animais , Coelhos , Canais de Cálcio Tipo L/metabolismo , Células Musculares/metabolismo , Sequência de Aminoácidos , Agonistas dos Canais de Cálcio/farmacologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Calmodulina/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Eletrofisiologia , Ventrículos do Coração/citologia , Ventrículos do Coração/metabolismo , Ativação do Canal Iônico/fisiologia , Ligantes , Dados de Sequência Molecular , Técnicas de Patch-Clamp , Peptídeos/farmacologia
4.
J. bras. nefrol ; 36(4): 512-518, Oct-Dec/2014. tab
Artigo em Inglês | LILACS | ID: lil-731151

RESUMO

Introduction: Tuberculosis is a common opportunistic infection in renal transplant patients. Objective: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. Methods: Retrospective and descriptive study. Results: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. Conclusion: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant. .


Introdução: A tuberculose é uma infecção oportunista comum em pacientes transplantados renais. Objetivo: Oferecer uma descrição clínica e laboratorial de pacientes transplantados com diagnóstico de tuberculose e sua resposta ao tratamento durante o período entre 2005 e 2013 no Hospital Pablo Tobón Uribe. Métodos: Estudo retrospectivo descritivo. Resultados: Em 641 transplantes renais, a tuberculose foi confirmada em 12 pacientes. Destes, 25% tinham histórico de rejeição aguda e 50% apresentaram níveis de creatinina superiores a 1,5 mg/dl antes da infecção. A patologia geralmente se apresentava como pulmonar (50%) e disseminada (33,3%). A primeira fase do tratamento consistiu de três meses de HZRE (isoniazida, pirazinamida, rifampicina e etambutol) em 75% dos casos e HZME (isoniazida, pirazinamida, moxifloxacina e etambutol) em 25% dos pacientes. Durante a segunda fase do tratamento, 75% dos pacientes receberam isoniazida e rifampicina e 25% isoniazida e etambutol. A duração do tratamento variou entre seis e 18 meses. Em 41,7% dos pacientes, hepatotoxicidade foi associada ao início do tratamento da tuberculose. Durante o seguimento de um ano a função renal manteve-se estável e a taxa de mortalidade foi de 16,7%. Conclusão: A tuberculose foi responsável por diversos sintomas inespecíficos na população de transplantados renais estudada. Tuberculose pulmonar e disseminada foram as formas mais frequentes de acometimento e necessitaram de tratamento prolongado. Medicamentos contra a tuberculose apresentaram alta toxicidade e mortalidade. Esta infecção deve ser considerada quando o paciente apresenta síndrome febril de origem desconhecida, especialmente durante o primeiro ano após o transplante renal. .


Assuntos
Animais , Feminino , Masculino , Camundongos , Locus Cerúleo/efeitos dos fármacos , Entorpecentes/farmacologia , Inibição Neural/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Canais de Potássio/metabolismo , Bário/farmacologia , Cálcio/metabolismo , Encefalina Metionina/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G , Proteínas de Ligação ao GTP/metabolismo , Heterozigoto , Homozigoto , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/fisiologia , Locus Cerúleo/citologia , Locus Cerúleo/fisiologia , Camundongos Knockout , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Técnicas de Patch-Clamp , Subunidades Proteicas , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/antagonistas & inibidores , Canais de Potássio Corretores do Fluxo de Internalização/deficiência , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Canais de Potássio/deficiência , Canais de Potássio/genética
5.
West Indian med. j ; 59(5): 473-478, Oct. 2010. tab
Artigo em Inglês | LILACS | ID: lil-672661

RESUMO

OBJECTIVE: The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa. METHODS: Swiss albino mice of either gender weighing between 25-30 g were used for the study. The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests. RESULTS: The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However, reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers. CONCLUSIONS: This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However, such interaction occurs at the level of potassium channels rather than at the level of receptors.


OBJETIVO: El estudio fue realizado para evaluar el efecto de los abridores de canales de potasio en la tolerancia a la morfina, y viceversa. MÉTODOS: Para el estudio, se usaron ratones albinos suizos de ambos sexos que pesaban entre 25-30 g. El estudio evalúa el efecto de los abridores de canales de potasio (cromacalina, diazóxido y minoxidil) en la tolerancia a la morfina, y viceversa, usando la prueba de la sacudida de la cola y la prueba de la formalina. RESULTADOS: El efecto antinociceptivo de la cromacalina y el minoxidil fue significativamente reducido cuando se le administró a los ratones tolerantes a la morfina, en ambas pruebas conductuales. Sin embargo, se observó un efecto analgésico reducido de diazóxido sobre la tolerancia a la morfina en la prueba de la formalina, pero no en la prueba de la sacudida de la cola. Se observó tolerancia al administrar morfina a animales crónicamente tratados con cualquiera de los abridores de canales de potasio. El mismo efecto fue observado cuando se inyectó la morfina al grupo tratado con una combinación de morfina y cualquiera de los abridores de canales de potasio. CONCLUSIONES: Por consiguiente, este estudio sugiere que tanto la morfina como los abridores de canales de potasio son tolerantes cruzados. Sin embargo, tal interacción ocurre a nivel de los canales de potasio más bien que a nivel de los receptores.


Assuntos
Animais , Camundongos , Analgésicos Opioides/farmacologia , Cromakalim/farmacologia , Tolerância a Medicamentos , Diazóxido/farmacologia , Minoxidil/farmacologia , Morfina/farmacologia , Canais de Potássio/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Modelos Animais , Dor
6.
Biol. Res ; 39(3): 385-401, 2006. ilus
Artigo em Inglês | LILACS | ID: lil-437374

RESUMO

Large conductance Ca2+-activated K+ (BK) channels belong to the S4 superfamily of K+ channels that include voltage-dependent K+ (Kv) channels characterized by having six (S1-S6) transmembrane domains and a positively charged S4 domain. As Kv channels, BK channels contain a S4 domain, but they have an extra (S0) transmembrane domain that leads to an external NH2-terminus. The BK channel is activated by internal Ca2+, and using chimeric channels and mutagenesis, three distinct Ca2+-dependent regulatory mechanisms with different divalent cation selectivity have been identified in its large COOH-terminus. Two of these putative Ca2+-binding domains activate the BK channel when cytoplasmic Ca2+ reaches micromolar concentrations, and a low Ca2+ affinity mechanism may be involved in the physiological regulation by Mg2+. The presence in the BK channel of multiple Ca2+-binding sites explains the huge Ca2+ concentration range (0.1 ìM-100 ìM) in which the divalent cation influences channel gating. BK channels are also voltage-dependent, and all the experimental evidence points toward the S4 domain as the domain in charge of sensing the voltage. Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca2+. Therefore, Ca2+ and voltage act independently to enhance channel opening, and this behavior can be explained using a two-tiered allosteric gating mechanism.


Assuntos
Animais , Canais de Cálcio/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/fisiologia , Regulação Alostérica/fisiologia , Ativação do Canal Iônico/fisiologia , Potenciais da Membrana/fisiologia
7.
Electron. j. biotechnol ; 7(2): 178-188, Aug. 2004. ilus, tab
Artigo em Inglês | LILACS | ID: lil-387556

RESUMO

Bacillus thuringiensis (Bt) is a valuable environment-friendly biopesticide, which occupies 90 percent of the world biopesticide market. Its insecticidal properties are attributed to the presence of delta-endotoxins which are synthesized during the sporulation phase of the bacterium. delta-endotoxin or crystal toxin is a multi-domain protein molecule comprising of three distinct domains. Domain I is made of seven alpha-helices, domain II comprises three antiparallel beta sheets, which are folded into loops and domain III is made of a beta sandwich of two antiparallel beta strands. Molecular studies on the structure and functional properties of different delta-endotoxins revealed that the domain I by virtue of its membrane spanning hydrophobic and amphipathic alpha-helices is capable of forming pores in the cell membranes of the larval midgut. Domain II being hyper variable in nature determines the insecticidal specificity of a toxin and domain III is involved in varied functions like structural stability, ion channel gating, binding to Brush Border Membrane Vesicles and insecticidal specificity. Recent studies on toxin aggregation and interaction revealed that the three domains interact closely to bring about the insecticidal activity of Bt. In this review we describe the protein engineering studies conducted on different delta-endotoxins which led to an understanding of their molecular mode of action and construction of novel toxins with enhanced insecticidal activity and specificity.


Assuntos
Bacillus thuringiensis , Engenharia de Proteínas , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Membrana Celular , Controle Biológico de Vetores/métodos , Condutividade Elétrica , Endotoxinas/metabolismo , Ativação do Canal Iônico , Bicamadas Lipídicas , Praguicidas
8.
Rev. sanid. mil ; 51(3): 141-9, mayo-jun. 1997. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-227350

RESUMO

En este artículo se revisan avances recientes sobre canales y corrientes iónicas del corazón. Los canales con complejos macromoleculares de proteínas que forman poros en la membrana celular, por los cuales pasan corrientes iónicas que se registran mediante técnicas de microárea de membrana (®pach clamp¼). Las proteínas de los canales consisten en la unión de cadenas polipeptídicas denominadas subunidades (o monómeros), constituidas a su vez por cuatro dominios y segmentos. La subunidad alfa (a) es la parte funcional del canal porque contiene el sensor de voltaje para las compuertas del canal y el sitio de unión para toxinas y fármacos que bloquean los canales. Hay una gran variedad de canales, en especial de K+, lo que se atribuye a diferentes genes o a genes mutantes, de los canales cardíacos. La actividad eléctrica del corazón se explica en función de las corrientes iónicas y de su modulación por efecto de ligandos específicos y por actividad de proteínas G. Lo anterior tiene implicaciones clínicas en la clasificación de las arritmias cardíacas y su tratamiento farmacológico


Assuntos
Antiarrítmicos , Canais de Cálcio , Membrana Celular , Coração/fisiologia , Estimulação Elétrica , Eletrofisiologia , Ativação do Canal Iônico , Cinética , Canais de Sódio
9.
Rev. costarric. cienc. méd ; 17(3): 49-58, set. 1996. ilus
Artigo em Espanhol | LILACS | ID: lil-238071

RESUMO

En este artículo, se revisa el mecanismo de respuesta celular para mensajeros que actúan por medio de receptores de membrana con canal iónico incorporado o de receptores intracelulares, también conocidos como esteroides. Los principales ligandos para los receptores con canal iónico son neurotransmisores que al cambiar la conductancia de la membrana celular a iones como el sodio, potasio, calcio y cloruro modifican la excitabilidad de las células blanco. Los receptores esteroides se localizan intracelularmente, en el citosol o en el núcleo. Las hormonas que actúan a través de este tipo de receptor después de penetrar la membrana celular forman un complejo con el receptor que regula la transcripción genética.


Assuntos
Membranas Intracelulares , Ativação do Canal Iônico , Receptores de GABA , Receptores de Glutamato , Receptores de Esteroides , Costa Rica
10.
Niterói; s.n; 1996. 74 p. ilus, tab, graf.
Tese em Português | LILACS | ID: lil-655776

RESUMO

Neste trabalho estudados a ação de TG, TFP e OUA (substâncias conhecidas por alterar o fluxo iônico da célula) sobre a expressão de dois antígenos de membrana, o CD25 e o CD69, em células ativadas por PHA e por TPA. O CD25 é a cadeia alfa do receptor de II-2 que se expressa na membrana algumas horas após a ativação. O CD69, membro da família das selectinas é rapidamente expresso após a ativação. Além do PHA e TPA,outra substância que que por si só levou a expressão de CD25 e de CD69 foi a TG...Estes dados parecem indicar um possível papel para o CD69 também na morte celular. Nós verificamos que um mesmo sinal PHA pode levar a dissociação de resposta para a expressão de CD25 e CD69 em uma mesma célula. Os nossos resultados, aliados aos dados da literatura, demonstrem o envolvimento de diferentes vias de ativação conduzindo à proliferação, à citotoxicidade e provavelmente à morte celular e a possibilidade de que um mesmo estímulo seja capaz de ativar mais de uma dessas vias.


Assuntos
Antígenos de Superfície , Ativação do Canal Iônico , Ouabaína , Tapsigargina , Antígeno Polipeptídico Tecidual , Trifluoperazina
11.
P. R. health sci. j ; 14(3): 199-209, sept. 1995.
Artigo em Inglês | LILACS | ID: lil-176806

RESUMO

This review describes and analyzes the evidence from studies using noncompetitive inhibitors of the nicotinic acetylcholine receptor that the receptor's ion channel is formed by the second transmembrane segment of all five receptor subunits. Inconsistencies in this generally accepted model are also presented and discussed


Assuntos
Animais , Antagonistas Colinérgicos/farmacologia , Canais Iônicos/efeitos dos fármacos , Receptores Colinérgicos/antagonistas & inibidores , Sequência de Aminoácidos , Ativação do Canal Iônico/efeitos dos fármacos , Sítios de Ligação , Canais Iônicos/metabolismo , Cátions/metabolismo , Modelos Químicos , Dados de Sequência Molecular , Neurotoxinas/farmacologia , Conformação Proteica , Receptores Colinérgicos/química , Receptores Colinérgicos/metabolismo
12.
Braz. j. med. biol. res ; 28(4): 491-6, Apr. 1995. ilus
Artigo em Inglês | LILACS | ID: lil-154851

RESUMO

Ion channels are protein molecules which can assume distinct open and closed conformational states. The transitions between these states can be controlled by the electrical field, ions and/or drugs. Records of unitary current events show that short open-time intervals are frequently adjacent to much longer closed-time intervals, and vice-versa, suggesting that the kinetic process has memory, i.e., the intervals are correlated in time. here the rescaled range analysis (R/S Hurst analysis) is proposed as a method to test for correlation. Simulations were performed with a two-state Markovian model, which has no memory. The calculated Hurst coefficients (H) presented a mean + or - SD value of 0.493 + or - 0.025 (N = 100). For the Ca2+ -activated K+ channels of Leydig cells, H wass equal to 0.75, statistically different (1 percent level) from that calculated for the memoryless proces. Randomly shuffling the experimental data resulted in an H = 0.55, not significantly different (1 percent level) from that found for the two-state Markovian model. For a linear three-state Markovian model, H was equal to 0.548 + or - 0.017 (N = 15), agin not significantly different (1 percent level) from that of the memoryless proces. Although the tree-state Markovian model adequately describes the open-and closed-time distributions, it does not account for the correlation found in this Ca2+ -activatedK+ channel. Our results ilustrate the efficacy of the R/S analysis in determining whether successive opening and closing events are correlated in time and can be of help in deciding which odel should be used to describe the kinetics of ion channels


Assuntos
Humanos , Animais , Camundongos , Canais Iônicos/fisiologia , Ativação do Canal Iônico , Cinética , Cadeias de Markov , Modelos Biológicos
13.
Anon.
Medicina (B.Aires) ; 55(5,pt.2): 591-599, 1995.
Artigo em Inglês | LILACS | ID: lil-321745

RESUMO

Ionic and gating currents from Shaker K+ channels were characterized with the cut-open oocyte voltage clamp (COVG) technique. Experiments were performed in normally conducting channels and in channels with the W434F mutation which completely abolished ion conduction without affecting the voltage dependence of gating charge. Subtracted and unsubtracted gating currents with the COVG technique, and gating currents recorded in cell attached macro-patches had the same properties and time course. However, OFF gating currents and ionic deactivation tails became slower after patch excision. Gating currents had the following salient properties: 1) the turn-on of the gating current shows a rising phase, 2) the more negative position of the charge-voltage curve (Q-V) vs. the conductance-voltage (G-V) curve and the charge displacement by hyperpolarizing prepulses indicate that a large fraction of the voltage-dependence occurs in the transitions between closed states, 3) the Q-V relationship showed two component with different half activation potential and effective valence; the one appearing at more negative potential had a shallower voltage dependence, while the one at more depolarized potentials had a larger effective valence and correlated with channel opening, 4) ionic and gating currents were similarly time shifted by preceding hyperpolarizing and depolarizing pulses which substantiates the relationship between charge movement and channel opening, 5) in the wild type Shaker K+ clone with fast inactivation, the OFF gating charge is partially immobilized for large depolarizing pulses, while in the mutant channel lacking inactivation the charge is recovered quickly at the end of the pulse, indicating that the channel blockade by the inactivating particle slows down charge recovery, 6) the OFF gating current rapidly returns for small depolarizations, while for larger pulses which open the channel the OFF gating current return is delayed suggesting that the closed to open transitions carry little charge and 7) in the W434F mutant with the conserved amino terminus large depolarizations that would have opened the channel induced OFF charge immobilization, indicating that although the conduction pathway was not functional, the channel can still undergo the closed-open conformation in response to voltage changes. In conclusion, the kinetic properties of gating currents discard equal and independent gating subunits with two positions.


Assuntos
Animais , Feminino , Ativação do Canal Iônico/fisiologia , Canais de Potássio/fisiologia , Potenciais da Membrana , Modelos Biológicos , Mutação , Oócitos , Técnicas de Patch-Clamp , Fatores de Tempo , Xenopus
15.
Braz. j. med. biol. res ; 26(6): 541-52, Jun. 1993. ilus, graf
Artigo em Inglês | LILACS | ID: lil-148708

RESUMO

1. Gap junction channels interconnect cells of the pacemaking, conduction and contraction elements of the heart and also endothelial and smooth muscle cells of vasculature, thereby providing pathways for electrotonic current spread and for second messenger diffusion. The major gap junction protein in the cardiovascular system is connexin43. 2. When human connexin43 is stably expressed in pairs of a communication-deficient cell line (SKHep1) channels are produced with unitary conductance (gamma j), lipophile sensitivity and voltage-dependent gating similar to those of mammalian systems in which connexin43 is endogenously expressed. 3. At moderate transjunctional voltages (Vj), two gamma j values dominated the recordings, about 60 and 90 pS with CsCl patch solution. The smaller channel size is favored by phosphorylating treatments and the larger channel, by dephosphorylating treatments. 4. Human connexin43 mutants truncated at the carboxy termini display a change in gamma j while a point mutation in the third transmembrane spanning domain appears to change channel selectivity. 5. Voltage dependence of the human connexin43 channel is marked at Vjs, above +/- 50 mV, but large residual conductance remains (due probably to a voltage-insensitive substate) even at the largest Vj values; kinetic but not steady-state behavior is affected by phosphorylation state


Assuntos
Humanos , Animais , Ratos , Conexinas/fisiologia , Ativação do Canal Iônico , Biofísica , Conexinas/metabolismo , Mutagênese , Miocárdio/citologia , Fosforilação , Sistemas do Segundo Mensageiro
16.
Braz. j. med. biol. res ; 26(6): 553-71, Jun. 1993. tab
Artigo em Inglês | LILACS | ID: lil-148709

RESUMO

The nicotinic acetylcholine receptor (AChR) is still the paradigm of rapid ligand-gated ion channels. Since the early finding of a motionally restricted shell of lipids ( annulus ) in the immediate perimeter of the membrane-bound AChR, experimental evidence has supported the notion that the interface between the protein moiety and the adjacent lipid molecules is the site of action of a variety of pharmacologically relevant substances, including non-competitive inhibitors of the cholinergic system like some local anesthetics, short-chain alcohols, and steroids. Patch-clamp data on cells expressing the AChR protein add another dimension to this knowledge, enabling correlations to be established between the chemical composition of lipid-modified cells and the functional properties (ligand binding, channel gating) of the receptor protein in situ


Assuntos
Animais , Ativação do Canal Iônico , Lipídeos de Membrana/metabolismo , Receptores Nicotínicos/metabolismo , Anestésicos/farmacologia , Colesterol/metabolismo , Colesterol/farmacologia , Dexametasona/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Ácidos Graxos não Esterificados/metabolismo , Ácidos Graxos não Esterificados/farmacologia , Ativação do Canal Iônico , Cinética , Lipídeos de Membrana/farmacologia , Receptores Nicotínicos
17.
Braz. j. med. biol. res ; 25(10): 983-98, 1992. ilus, graf
Artigo em Inglês | LILACS | ID: lil-134655

RESUMO

1. Potassium channel opening drugs (KCOs) include benzopyrans such as cromakalim, cyanoguanidines such as pinacidil and tetrahydrothiopyrans such as RP 49356. 2. While clinical trials have indicated that cromakalim may be of benefit in the treatment of nocturnal asthma, it remains to be determined whether KCOs will find a place in our armamentarium of clinically useful anti-asthma agents. 3. KCOs inhibit the spontaneous tone of airways smooth muscle in vitro, an action associated with membrane hyperpolarization towards the potassium equilibrium potential and with the promotion of 86Rb+ or 42K+ efflux from the muscle cells. KCOs suppress spasm of airways smooth muscle evoked by low (< 40 mM) but not high (> 40 mM) concentrations of KCl. Their relaxant effects in airways smooth muscle can be attenuated by a variety of agents (including sulphonylureas) known to inhibit the opening of plasmalemmal K(+)-channels. 4. The KCOs open an ATP-sensitive K(+)-channel (KATP) in the plasmalemma. KATP is not open under normal circumstances and does not play an important role in determining the strong outward rectifying behavior of the cell membrane. The biochemical mechanisms by which the KCOs promote the opening of KATP remain to be elucidated but probably do not involve channel phosphorylation consequent to the intracellular accumulation of cAMP. 5. By causing hyperpolarization of the plasmalemma, the KCOs inhibit the cellular influx of Ca2+ through voltage-dependent channels. Relaxation follows both as a direct consequence of the fall in cytosolic free Ca2+ and also as a consequence of reduced production of phosphoinositide second messengers. The KCOs may also inhibit Ca2+ uptake by, and hence Ca2+ release from, the sarcoplasmic reticulum. 6. KCOs can inhibit cholinergic and non-adrenergic, non-cholinergic (NANC) excitatory neuroeffector transmission in the airways by glibenclamide-sensitive mechanisms which may involve inhibition of neurotransmitter release. The KCOs do not attenuate NANC inhibitory neuroeffector transmission, suggesting that KATP may not be expressed in neurones of this type. 7. The active enantiomer of cromakalim has been found to be effective in alleviating nocturnal asthma at plasma concentrations just threshold for relaxing human airways smooth muscle in vitro. The clinical efficacy of cromakalim may therefore depend on an action other than the direct relaxation of airways smooth muscle. Animal studies indicate that KCOs can reduce airway hyper-reactivity at sub-bronchodilator doses. The mechanism of this effect remains to be elucidated and may not crucially depend upon inhibition of neurotransmitter release within the lung


Assuntos
Animais , Brônquios/efeitos dos fármacos , Técnicas In Vitro , Ativação do Canal Iônico/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Benzopiranos/farmacologia , Brônquios/fisiologia , Broncodilatadores/farmacologia , Ativação do Canal Iônico/fisiologia , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Canais de Potássio/fisiologia , Pirróis/farmacologia
18.
Mem. Inst. Oswaldo Cruz ; 86(suppl. 2, n.esp): 169-71, Oct. 1991. tab
Artigo em Inglês | LILACS | ID: lil-127849

RESUMO

In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD) receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB), an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mer exposure to the training apparatus


Assuntos
Animais , Feminino , Ratos , Aprendizagem da Esquiva/efeitos dos fármacos , Benzodiazepinas/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Ativação do Canal Iônico , Benzodiazepinas/metabolismo , Diazepam/farmacologia , Proteínas de Membrana/efeitos dos fármacos , Ratos Endogâmicos , Receptores de GABA-A/fisiologia
19.
Mem. Inst. Oswaldo Cruz ; 86(supl.2): 169-171, 1991. tab
Artigo em Inglês | LILACS | ID: lil-623963

RESUMO

In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD) receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB), an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mere exposure to the training apparatus.


Assuntos
Animais , Ratos , Benzodiazepinas/metabolismo , Benzodiazepinas/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/fisiologia , Diazepam/farmacologia , Proteínas de Membrana/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Ratos Wistar , Canais de Cloreto
20.
Acta physiol. pharmacol. latinoam ; 37(4): 555-63, 1987. tab
Artigo em Inglês | LILACS | ID: lil-86923

RESUMO

Pos y Pd, los coeficientes de permeabilidad osmótica y difusiva al agua, de túbulos proximales (TP) de conejo (por cm**2 de membrana celular real, micronm/s) son Pos, 396; Pd, 22; Pos/Pd, 18 (controles). Con paracloromercuribencenosulfonato son Pos, 32; Pd, 10; Pos/Pd, 3. El reactivo de grupos sulfhidrilos ditiotreitol (DTT) revierte la acción del pCMBS. Las energías de activación (Kcal/mol) son Pos, 3.2 (controles); 9.2 (pCMBS); Pd, 5.2 (controles, 9.1 (pCMBS). Por lo tanto, canales acuosos atraviesan la membrana celular control y son cerrados por pCMBS. Las altas permeabilidades de TP (controles) son similares a las de la vejiga urinaria de anfibio (un análogo del túbulo colector, TC), estimulada con hormona antidiurética (ADH) y los valores bajos con pCMBS en TP recuerdan los de TC en reposo (sin ADH). La permeabilidad transcelular puede ser regulada por el estado de grupos sulfhidrilo en TP y por la adición de canales acuosos por la HAD (o su supresión, reposo). En T.P.(a) no-electrólitos extracelulares son arrastrados por el flujo de agua indicando interacción extracelular aguasoluto; (b) la Pos transepitelial es mucho mayor que la transcelualr. Por consiguiente, en adición al flujo transcelular hay flujo paracelular de agua. La permeabilidad en TP se incrementa si la urea luminal es mayor que la sanguínea (en 15-50 mM) y se reduce en la situación inversa. En TD (control) la permeabilidad paracelular es cero. Se incrementa con urea en condición control en TP y muy pequeña en TC...


Assuntos
Animais , Água Corporal/metabolismo , Permeabilidade da Membrana Celular/fisiologia , Túbulos Renais Coletores/fisiologia , Túbulos Renais Proximais/fisiologia , Túbulos Renais/fisiologia , Bexiga Urinária/fisiologia , Ativação do Canal Iônico/fisiologia , Canais Iônicos/fisiologia , Epitélio/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Concentração Osmolar , Transporte Biológico Ativo/fisiologia
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