Regulation of kidney on potassium balance and its clinical significance / 生理学报

Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na+ by the epithelial Na+ channel (ENaC) located at the apical membrane of principal cells. When Na+ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K+ efflux, H+ efflux, and Cl- influx are the 3 pathways that respond to Na+ influx, that is, all these 3 pathways are coupled to Na+ influx. In general, Na+ influx is equal to the sum of K+ efflux, H+ efflux, and Cl- influx. Therefore, any alteration in Na+ influx, H+ efflux, or Cl- influx can affect K+ efflux, thereby affecting the renal K+ excretion. Firstly, Na+ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na+ reabsorption, K+ excretion, as well as H+ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na+ and decreased excretion of both K+ and H+, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na+ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na+-K+-2Cl- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na+-Cl- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na+ by ENaC at the collecting duct, as well as increased excretion of K+ and H+, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H+ decreases. Both above conditions can lead to increased K+ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.

Activation of renal outer medullary potassium channel in the renal distal convoluted tubule by high potassium diet / 生理学报

Renal outer medullary potassium (ROMK) channel is an important K+ excretion channel in the body, and K+ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K+ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na+-Cl- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.

Contribution of dark septate fungi to the nutrient uptake and growth of rice plants

ABSTRACT The use of dark septate fungi (DSE) to promote plant growth can be beneficial to agriculture, and these organisms are important allies in the search for sustainable agriculture practices. This study investigates the contribution of dark septate fungi to the absorption of nutrients by rice plants and their ensuing growth. Four dark septate fungi isolates that were identified by Internal transcribed spacer phylogeny were inoculated in rice seeds (Cv. Piauí). The resulting root colonization was estimated and the kinetic parameters Vmax and Km were calculated from the nitrate contents of the nutrient solution. The macronutrient levels in the shoots, and the NO3--N, NH4+-N, free amino-N and soluble sugars in the roots, sheathes and leaves were measured. The rice roots were significantly colonized by all of the fungi, but in particular, isolate A103 increased the fresh and dry biomass of the shoots and the number of tillers per plant, amino-N, and soluble sugars as well as the N, P, K, Mg and S contents in comparison with the control treatment. When inoculated with isolates A103 and A101, the plants presented lower Km values, indicating affinity increases for NO3--N absorption. Therefore, the A103 Pleosporales fungus presented the highest potential for the promotion of rice plant growth, increasing the tillering and nutrients uptake, especially N (due to an enhanced affinity for N uptake) and P.

Governo local e serviços odontológicos: análise da desigualdade na utilização / Local government and public dental health services: an analysis of inequality in use / Gobierno local y servicios odontológicos: análisis de la desigualdad en el uso

O objetivo deste estudo foi identificar fatores associados à utilização dos serviços odontológicos, públicos (básicos e especializados) e privados. Foi realizado inquérito populacional de base domiciliar em dois municípios da Bahia, Brasil. Informantes-chave forneceram dados socioeconômicos e de utilização dos serviços odontológicos (desfecho). A organização do serviço público odontológico local foi classificada em pior/melhor. Realizou-se regressão logística politômica uni e múltipla. Do total de 1.290 indivíduos, 38,76% usaram o serviço privado, 33,80% atenção básica e 17,29% atenção básica e o Centro de Especialidades Odontológicas (CEO). Um perfil de vulnerabilidade social foi associado ao uso do serviço público, quando comparado ao privado. Menor escolaridade (OR = 1,47; IC95%: 1,03-2,10) e pior organização do serviço (OR = 1,74; IC95%: 1,22-2,48) foram associados ao menor uso da rede de serviços atenção básica e CEO em comparação ao uso exclusivo da atenção básica. A desigualdade na utilização dos serviços odontológicos foi observada mesmo quando comparados grupos mais homogêneos, como os usuários dos serviços públicos.

The aim of this study was to identify factors associated with the use of primary and specialized public dental health services and private services. A population-based household survey was conducted in two cities of Bahia State, Brazil. Key informants provided data on socioeconomic variables and use of dental health services. Organization of the local public dental health service was ranked as worse versus better. Univariate and multivariate polytomous logistic regression was performed. Of the total of 1,290 individuals, 38.76% used private services, 33.80% used public primary care, and 17.29% used both primary care and the Center for Dental Specialties. Less use of both primary care and specialized public services was associated with lower education (OR = 1.47; 95%CI: 1.03-2.10) and worse organization of services (OR = 1.74; 95%CI: 1.22-2.48), when compared to the exclusive use of primary care. The study showed inequality in the use of dental services, even when comparing more homogeneous groups, namely users of public services.

El objetivo de este estudio fue identificar los factores asociados al uso de los servicios odontológicos (primarios y especializados) públicos y privados. Se realizó una encuesta poblacional en dos ciudades de Bahía, Brasil. Los informantes clave contestaron cuestiones socioeconómicas y de utilización de los servicios odontológicos (resultado). La organización de los servicios odontológicos públicos locales fue clasificada en peor/mejor. Se realizó regresión simple y múltiple con variable politómica. Del total de 1.290 personas, un 38,76% utilizaron el servicio privado, un 33,80% la atención primaria y un 17,29% atención primaria y el Centro de Especialidades Dentales (CED). Una menor escolaridad (OR = 1,47; IC95%: 1.03-2.10) y una peor organización de servicio (OR = 1,74; IC95%: 1,22-2,48) se asociaron con un menor uso de la red de servicios de atención primaria y CED, en comparación con el uso exclusivo de la atención primaria. La desigualdad en el uso de los servicios dentales se observó incluso cuando se comparan grupos más homogéneos, como usuarios de servicios públicos.

In vitro response of date palm (Phoenix dactylifera L) to K/Na ratio under saline conditions

BACKGROUND: Salinity is a serious factor limiting the productivity of agricultural plants. One of the potential problems for plants growing under saline conditions is the inability to up take enough K+. The addition of K+ may considerably improve the salt tolerance of plants grown under salinity. It is assumed that increasing the K+ supply at the root zone can ameliorate the reduction in growth imposed by high salinity. The present study aims to determine whether an increase in the K/Na ratio in the external media would enhance the growth of date palm seedlings under in vitro saline conditions. METHODS: Date palm plants were grown at four concentrations of Na + K/Cl (mol/m³) with three different K/Na ratios. The 12 salt treatments were added to modified MS medium. The modified MS medium was further supplemented with sucrose at 30 g/l. RESULTS: Growth decreased substantially with increasing salinity. Growth expressed as shoot and root weight, enhanced significantly with certain K/Na ratios, and higher weight was maintained in the presence of equal K and Na. It is the leaf length, leaf thickness and root thickness that had significant contribution on total dry weight. Na+ contents in leaf and root increased significantly increased with increasing salinity but substantial decreases in Na+ contents were observed in the leaf and root with certain K/Na ratios. This could be attributed to the presence of a high K+ concentration in the media. The internal Na+ concentration was higher in the roots in all treatments, which might indicate a mechanism excluding Na+ from the leaves and its retention in the roots. K/Na ratios up to one significantly increased the leaf and root K+ concentration, and it was most pronounced in leaves. The K+ contents in leaf and root was not proportional to the K+ increase in the media, showing a high affinity for K+ uptake at lower external K+ concentrations, but this mechanism continues to operate even with high external Na+ concentrations. CONCLUSION: Increasing K/Na ratios in the growing media of date plam significantly reduced the absorption of Na+ less than 200 mM and also balance ions compartmentalization.

Fração de excreção de potássio na evolução da lesão renal aguda em pacientes graves: um potencial marcador a ser monitorizado? / Fractional excretion of potassium in the course of acute kidney injury in critically ill patients: potential monitoring tool?

Objetivo: Avaliar o comportamento da fração de excreção de potássio durante a evolução da lesão renal aguda em pacientes graves. Métodos: Foram incluídos 168 pacientes como parte de um estudo maior, no qual avaliamos parâmetros sanguíneos e urinários durante a evolução da lesão renal aguda. Foram coletadas diariamente amostras de sangue e urina até a remoção da sonda vesical ou a necessidade de terapia de substituição renal. Descrevemos a evolução da fração de excreção de potássio conforme a presença ou não de lesão renal aguda, sua duração - transitória ou persistente - e gravidade (com base no estágio Acute Kidney Injury Network - AKIN). Foi também avaliado o desempenho diagnóstico da fração de excreção de potássio no dia do diagnóstico da lesão renal aguda, para prever a sua duração e a necessidade de terapia de substituição renal. Resultados: A fração de excreção de potássio foi significativamente maior na lesão renal aguda persistente do que na transitória no dia do diagnóstico da lesão renal aguda (24,8 versus 13,8%; p<0,001). Ambos os grupos tiveram aumento de sua fração de excreção de potássio mediana nos 2 dias que precederam o diagnóstico de lesão renal aguda. Pacientes que não desenvolveram mantiveram níveis baixos e estáveis de fração de excreção de potássio. A fração de excreção de potássio, no dia do diagnóstico de lesão renal aguda, demonstrou razoável precisão em prever lesão renal aguda persistente (área sob a curva: 0,712; intervalo de confiança de 95%: 0,614-0,811; p<0,001). A área sob ...

Objective: To evaluate the behavior of fractional excretion of potassium in the course of acute kidney injury in critically ill patients. Methods: As part of a larger study in which we have evaluated blood and urinary parameters in the course of acute kidney injury, 168 patients were included. Blood and urine samples were collected daily until the removal of the urinary catheter or the initiation of renal replacement therapy. We describe the evolution of fractional excretion of potassium based on whether acute kidney injury was diagnosed, its duration (transient or persistent) and its severity (creatinine-based Acute Kidney Injury Network - AKIN stage). The diagnostic performance of fractional excretion of potassium in predicting the duration of acute kidney injury and the need for renal replacement therapy on the day of acute kidney injury diagnosis was also evaluated. Results: Fractional excretion of potassium was significantly higher in persistent acute kidney injury compared to transient acute kidney injury on the day of acute kidney injury diagnosis (24.8 vs. 13.8%, p<0.001). Both groups had the median fractional excretion of potassium increasing in the two days preceding the acute kidney injury diagnosis. Patients without acute kidney injury had stable low fractional excretion of potassium values. The fractional excretion of potassium was fairly accurate in predicting persistent acute kidney injury (area under the curve: 0.712; 95% confidence interval: 0.614-0.811; p<0.001) on the day of acute kidney injury diagnosis. The area under the curve was 0.663 (95% confidence interval: 0.523-0.803; p=0.03) for renal replacement therapy. The fractional excretion of potassium increased with maximum AKIN stage reached, in both transient and persistent acute kidney injury. Conclusion: Sequential fractional excretion of potassium assessment appears to be useful in critically ill patients at risk for acute kidney injury. .

Incorporation of Na+/H+ antiporter gene from Aeluropus littoralis confers salt tolerance in soybean (Glycine max L.).

To develop a salt-tolerant soybean (Glycine max L.) cultivar, a minimal linear Na+/H+ antiporter gene cassette (35S CaMV promoter, open-reading-frame of AlNHX1 from Aeluropus littoralis and NOS terminator) was successfully expressed in soybean cultivar TF-29. Southern and Northern blot analysis showed that AlNHX1 was successfully incorporated into the genome and expressed in the transgenic plants. The AlNHX1 transgenic plant lines exhibited improved growth in severe saline condition (150 mM NaCl). The transgenic lines accumulated a lower level of Na+ and a higher level of K+ in the leaves than wild-type plants under saline condition (150 mM NaCl). Observations on the chlorophyll content, photosynthetic rates, malondialdehyde and relative electrical conductivity indicated that transgenic plants exhibited tolerance to salt stress, growing normally at salt concentrations up to 150 mM. These results demonstrated that AlNHX1 was successfully transferred into soybean and the salt-tolerance was improved by the overexpression of AlNHX1.

Entendendo os distúrbios hidroeletrolíticos e o equilíbrio ácido-básico / Understanding hydroeletrolytic disturbances and acid-basic balance

Os distúrbios hidroeletrolíticos e o equilíbrio ácido-básico são frequentes no dia a dia de especialidades clínicas e cirúrgicas. O entendimento da sua fisiopatologia é essencial para o seu tratamento adequado. Este artigo discursa sobre os distúrbios hidroeletrolíticos e os do equilíbrio ácido-básico mais comuns.

Electrolyte disorders and acid-base balance occur on a daily basis in both clinical and surgical specialties. The pathophysiological understanding of these disorders is essential for their appropriate treatment. This article addresses the most common electrolyte and acid-base disorders.

Potássio menor que 3.5 ou maior que 4.5 aumenta mortalidade em pacientes hospitalizados por infarto agudo do miocárdio / Potassium less than 3.5 or greater than 4.5 increases mortality in patients hospitalized for acute myocardial infarction

Para pacientes internados por infarto agudo do miocárdio,níveis de potássio menores do que 3,5 mEq/l ou maiores doque 4,5 mEq/l estão associados a maior mortalidade durante ainternação. Ainda não está estabelecido se isso é uma evidênciade relação causal ou um mero sinal de gravidade da doença. Astaxas de arritmias ventriculares e de paradas cardíacas forammaiores com níveis de potássio mais extremos (menores do que3,0 mEq/l ou maiores do que 5,0 mEq/l).

Latest progress in postmortem interval estimation / 法医学杂志

Accurate estimation of the postmortem interval (PMI) has been one of the most important and complicated issues in the forensic practice. In order to provide novel perspectives for the future research concerning PMI, the advantages and disadvantages of related traditional methods, postmortem degradation of nucleic acid and tissue, the componential change of vitreous humor and histological biochemistry since 2002 have been introduced and compared in this review.

Sodio, potasio e hipertensión arterial / Sodium, potassium and hypertension

La hipertensión arterial tiene una prevalencia cercana al 30 por ciento en la población adulta chilena y es la mayor causa de muerte en el mundo. La hipertensión primaria resulta de la interacción de distintos factores tanto genéticos, como funcionales renales y en particular un estilo de vida poco saludable. En este artículo se describe la influencia del exceso de sodio y el déficit de potasio, característicos de nuestra alimentación, en el desarrollo de hipertensión. Se revisan los estudios observacionales más importantes, los mecanismos fisiopatológicos para explicar el rol dañino del exceso de sodio y el déficit de potasio y finalmente se hacen recomendaciones para adecuar su consumo con el fin de prevenir hipertensión y sus complicaciones.

Arterial hypertension has a prevalence of about 30 percent in the adult Chilean population and it is the major cause of mortality worldwide. Primary hypertension results from the interaction of genetic factors, functional renal impairment and particularly from an altered life style. This article describes the impact of the excess of sodium and the deficit of potassium of our usual alimentation in the development of hypertension. In this setting, some important observational studies and physiopathological mechanisms were discussed, and finally some recommendations to reduce sodium and to increase potassium intake to prevent hypertension and vascular complications, were made.

Role of 11â-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure

Aldosterone concentrations vary in advanced chronic renal failure (CRF). The isozyme 11â-hydroxysteroid dehydrogenase 2 (11â-HSD2), which confers aldosterone specificity for mineralocorticoid receptors in distal tubules and collecting ducts, has been reported to be decreased or normal in patients with renal diseases. Our objective was to determine the role of aldosterone and 11â-HSD2 renal microsome activity, normalized for glomerular filtration rate (GFR), in maintaining K+ homeostasis in 5/6 nephrectomized rats. Male Wistar rats weighing 180-220 g at the beginning of the study were used. Rats with experimental CRF obtained by 5/6 nephrectomy (N = 9) and sham rats (N = 10) were maintained for 4 months. Systolic blood pressure and plasma creatinine (Pcr) concentration were measured at the end of the experiment. Sodium and potassium excretion and GFR were evaluated before and after spironolactone administration (10 mg·kg-1·day-1 for 7 days) and 11â-HSD2 activity on renal microsomes was determined. Systolic blood pressure (means ± SEM; Sham = 105 ± 8 and CRF = 149 ± 10 mmHg) and Pcr (Sham = 0.42 ± 0.03 and CRF = 2.53 ± 0.26 mg/dL) were higher (P < 0.05) while GFR (Sham = 1.46 ± 0.26 and CRF = 0.61 ± 0.06 mL/min) was lower (P < 0.05) in CRF, and plasma aldosterone (Pald) was the same in the two groups. Urinary sodium and potassium excretion was similar in the two groups under basal conditions but, after spironolactone treatment, only potassium excretion was decreased in CRF rats (sham = 0.95 ± 0.090 (before) vs 0.89 ± 0.09 µEq/min (after) and CRF = 1.05 ± 0.05 (before) vs 0.37 ± 0.07 µEq/min (after); P < 0.05). 11â-HSD2 activity on renal microsomes was lower in CRF rats (sham = 0.807 ± 0.09 and CRF = 0.217 ± 0.07 nmol·min-1·mg protein-1; P < 0.05), although when normalized for mL GFR it was similar in both groups. We conclude that K+ homeostasis is ...

The synergetic modulation of the excitability of central gray matter by a neuropeptide: two protocols using excitation waves in chick retina

The isolated chick retina provides an in vitro tissue model, in which two protocols were developed to verify the efficacy of a peptide in the excitability control of the central gray matter. In the first, extra-cellular potassium homeostasis is challenged at long intervals and in the second, a wave is trapped in a ring of tissue causing the system to be under self-sustained challenge. Within the neuropil, the extra-cellular potassium transient observed in the first protocol was affected from the initial rising phase to the final concentration at the end of the five-minute pulse. There was no change in the concomitants of excitation waves elicited by the extra-cellular rise of potassium. However, there was an increase on the elicited waves latency and/or a rise in the threshold potassium concentration for these waves to appear. In the second protocol, the wave concomitants and the propagation velocity were affected by the peptide. The results suggest a synergetic action of the peptide on glial and synaptic membranes: by accelerating the glial Na/KATPase and changing the kinetics of the glial potassium channels, with glia tending to accumulate KCl. At the same time, there is an increase in potassium currents through nerve terminals.

Retinas de pinto isoladas proporcionam um modelo de tecidos in vitro, para o qual dois protocolos foram desenvolvidos para verificar a eficácia de um peptídeo no controle da excitabilidade da matéria cinzenta central. No primeiro, a homeostase do potássio extra-celular é desafiada por intervalos longos (1 hora) e no segundo, uma onda é capturada em um anel de tecido, de tal maneira que o sistema permaneça em estado de desafio auto-sustentado. Dentro da neuropil, o transiente de potássio extra-celular observado no primeiro protocolo foi afetado da fase de início de aumento à concentração final, ao final do pulso de cinco minutos. Não há mudanças nos parâmetros concomitantes das ondas de excitação geradas pelo aumento do potássio extra-celular. Entretanto, houve um aumento da latência das ondas geradas e/ou um aumento no nível de concentração de potássio necessário para gerar a onda. No segundo protocolo, os parâmetros concomitantes da onda e sua velocidade de propagação foram afetados pelo peptídeo. Os resultados sugerem uma ação sinergética do peptídeo nas membranas gliais e sinápticas: acelerando o Na/KATPase glial e mudando a cinética dos canais de potássio gliais, com a glia tendendo a acumular KCl. Nesse período, não há aumento nas correntes de potássio nas terminações nervosas.

Regulation of Antiarrhythmic Drug Propafenone Effects on the C-type KV1.4 Potassium Channel by PHo and K+

The effects of the antiarrhythmic drug propafenone at c-type kv1.4 channels in Xenopus laevis oocytes were studied with the two-electrode voltage-clamp techinique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4 delta N channels. During recording, oocytes were continuously perfused with control solution or propafenone. Propafenone decreased the currents during voltage steps. The block was voltage-, use-, and concentration- dependent manners. The block was increased with positive going potentials. The voltage dependence of block could be fitted with the sum of monoexponential and a linear function. Propafenone accelerated the inactivate of current during the voltage step. The concentration of half-maximal block (IC(50)) was 121 micrometer/L. With high, normal, and low extracellular potassium concentrations, the changes of IC(50) value had no significant statistical differences. The block of propafenone was PH- dependent in high-, normal- and low- extracellular potassium concentrations. Acidification of the extracellular solution to PH 6.0 increased the IC50 values to 463 micrometer/L, alkalization to PH 8.0 reduced it to 58 micrometer/L. The results suggest that propafenone blocks the kv1.4 delta N channel in the open state and give some hints for an intracellular site of action.

Disorders of potassium homeostasis: pathophysiology and management.

Disorders of potassium homeostasis are common electrolyte abnormalities encountered in hospitalized patients. Hypokalemia and hyperkalemia have been estimated to occur in about 21% and 3% of hospitalized patients, respectively; though the morbidity and mortality associated with the latter is significantly higher. Potassium is a predominantly intracellular ion and the understanding of its dynamics between intra- and extracellular fluid milieus, along with its handling by the kidneys, is important in the diagnosis and treatment of potassium disorders. This article aims to provide a clinically relevant update on management of potassium disorders for internists.

Propriedades Redox de canais de potássio mitocondriais ATP-sensíveis em cérebro e seu efeito neuroprotetor em excitotoxicidade / Redox properties of brain mitochondrial ATP-sensitive potassium channels and neuroprotective effects in excitotoxicity

Muitos estudos demonstram que a abertura de canais de ´KPOT.+` mitocondriais sensíveis à ATP (mito´K ind.ATP`) previnem contra danos promovidos por isquemia/reperfusao em coração. Em geral, esta proteçao envolve mudanças no estado redox mitocondrial. Em cérebro, sabe-se que agonistas farmacológicos de mito´K ind.ATP` também protegem em modelo de isquemia/reperfusão. Entretanto, os mecanismos envolvidos na prevenção de danos em cérebro ainda não estão claros. 0 objetivo principal deste trabalho é compreender os efeitos de canais de K+ mitocondriais ATP-sensíveis em tecido cerebral e os mecanismos pelos quais a sua ativação pode proteger contra danos promovidos por excitotoxicidade, uma das principais consequências de um evento isquêmico em cerebro. Neste contexto, demonstramos a proteção pelo mito´K ind.ATP` em modelo de excitotoxicidade induzida pela ativação direta de receptores NMDA, utilizando cultura de células granulosas de cerebelo. Paralelamente a essa proteção, verificamos que a ativação de mito´K ind.ATP` reduz a geração de espécies reativas de oxigênio (ROS)...