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1.
Ecotoxicol Environ Saf ; 211: 111904, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33453639

RESUMEN

This original research was performed to assess the possible effects of solid biochar (25 g biochar kg-1 soil) and biochar-based nanocomposites (BNCs) of magnesium oxide (25 g BNC-MgO kg-1 soil), manganese oxide (25 g BNC-MnO biochar kg-1 soil) and combined use of these nanocomposites (12.5 g BNC-MgO + 12.5 g BNC-MnO kg-1 soil) on soil properties and salinity (non-saline, 6 and 12 dSm-1) tolerance of safflower plants (Carthamus tinctorius L.). Application of biochar, particularly BNCs increased the pH and cation exchange capacity of soil, and the contents of water, potassium, calcium, magnesium, manganese, chlorophyll (a & b), nutrients uptake, water use efficiency and plant growth. Sodium adsorption ratio (SAR), exchangeable sodium percentage (ESP) of soil, sodium absorption rate of plants and osmolyte production (soluble carbohydrates and proteins, proline and glycine betaine) under 6 and 12 dSm-1 salinities were decreased by biochar and BNCs treatments. Sodium sorption capacity of BNCs was much higher than the solid biochar, which reflected the superiority of BNCs in decreasing sodium uptake by plants. The combined application of BNC-MgO + BNC-MnO proved to be the preferable treatment for decreasing salt toxicity in safflower. Biochar and BNCs improved root and shoot growth by lowering SAR, ESP, sodium absorption rate of plants and osmotic stress under saline conditions. These results conclude that BNCs can enrich the plant cells with nutrients, increase the nutrients absorption rate and maintain the plant tissue water content at an optimum level to improve plant growth under salt stress.


Asunto(s)
Carbón Orgánico , Magnesio/química , Manganeso/química , Adsorción , Carthamus tinctorius/metabolismo , Clorofila , Iones/metabolismo , Magnesio/metabolismo , Manganeso/metabolismo , Nanocompuestos , Óxidos/metabolismo , Potasio/metabolismo , Salinidad , Estrés Salino , Tolerancia a la Sal , Sodio/metabolismo , Suelo/química , Contaminantes del Suelo/metabolismo
2.
Ecotoxicol Environ Saf ; 211: 111901, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33453640

RESUMEN

The effects of fullerenol nanopriming (0, 10, 40, 80 and 120 nM concentration) on salt stressed-wheat (0 and 150 mM NaCl) were investigated under natural conditions. Salinity resulted in a shift in wheat growth pattern in the form of LAR (+ 40.9% increase) and RGR (+ 13.4% increase) while decreased NAR (- 31.7%). It also disturbed shoot and root biomass, ion uptake and reduced chlorophyll contents. Despite increase in enzyme activities, higher ROS generation (+ 48.1% O2- anion; and + 62.2% H2O2) and lipid peroxidation (+ 40.8% MDA) were detected in salt-stressed wheat plants. Possibly, the increases in enzyme activities were not up to the level to completely counteract the salinity induced oxidative stress. Nanopriming with fullerenol improved NAR (+ 8.77% to 23.2%), ROS metabolism and decreased indicators of oxidative stress. Hydropriming treatment also promoted NAR recovery by 21.9% than control plants. Compared to Na+ ions, improvements in shoot relative concentrations of K+, Ca2+ and P also recorded along with soluble sugars and amino acids, which improved osmotic balance. These biochemical modifications contributed to improvements in grain yield attributes (+11.8% to 18.3% in 100 grain-weight) than salinity stressed control. Hydropriming also contributed to a recovery in grain yield attributes by 12.6%. Above all, the harvested seeds from fullerenol treated plants also showed better germination and seedlings growth traits. Conclusively, we report non-toxic, growth-promoting effects of fullerenol nanoparticles on wheat crop and as a way forward; we suggest its exogenous application to recover crop productivity under saline environments.


Asunto(s)
Fulerenos/metabolismo , Estrés Oxidativo/fisiología , Estrés Salino/fisiología , Triticum/fisiología , Antioxidantes/metabolismo , Clorofila/metabolismo , Germinación/efectos de los fármacos , Homeostasis/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Iones/metabolismo , Peroxidación de Lípido , Salinidad , Estrés Salino/efectos de los fármacos , Plantones/efectos de los fármacos , Semillas/metabolismo , Sodio/metabolismo , Triticum/crecimiento & desarrollo
3.
Nat Commun ; 12(1): 128, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397917

RESUMEN

Voltage-gated sodium (NaV) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac NaV1.5 channels with IC50 = 11.4 nM. Here we reveal the structure of LqhIII bound to NaV1.5 at 3.3 Å resolution by cryo-EM. LqhIII anchors on top of voltage-sensing domain IV, wedged between the S1-S2 and S3-S4 linkers, which traps the gating charges of the S4 segment in a unique intermediate-activated state stabilized by four ion-pairs. This conformational change is propagated inward to weaken binding of the fast inactivation gate and favor opening the activation gate. However, these changes do not permit Na+ permeation, revealing why LqhIII slows inactivation of NaV channels but does not open them. Our results provide important insights into the structural basis for gating-modifier toxin binding, voltage-sensor trapping, and fast inactivation of NaV channels.


Asunto(s)
Miocardio/metabolismo , Canal de Sodio Activado por Voltaje NAV1.5/química , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Venenos de Escorpión/toxicidad , Animales , Sitios de Unión , Microscopía por Crioelectrón , Células HEK293 , Humanos , Activación del Canal Iónico/efectos de los fármacos , Simulación de Dinámica Molecular , Canal de Sodio Activado por Voltaje NAV1.5/ultraestructura , Conformación Proteica , Ratas , Venenos de Escorpión/química , Sodio/metabolismo
4.
Food Chem ; 338: 127840, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-32822903

RESUMEN

In bottled wines, haze and turbidity are phenomena to be avoided. Since bentonite fining is a common process to clarify wines removing heat unstable proteins, a theoretical study on the adsorption of three Charged Model Molecules (CMMs, egg albumin, polyphenols and riboflavin) was carried out to deep comprehend this chemical phenomenon. Four bentonites were adopted and finely characterized together with the potential release of Na+ and Ca2+ cations, revealing suitable for RT albumin removal within 120 min. Better results in terms of adsorbed quantity were achieved by adopting 12%v/v EtOH/H2O solvent and by swelling bentonites for 24 h before use. With the most performing sample (Na/Ca_0.27), a comprehensive study on simultaneous adsorption of the three CMMs was performed, resulting in polyphenols adsorption increase due to their interactions with albumin. Notwithstanding the majority of albumin and riboflavin was successfully removed, ca. 40-50% of tested polyphenols was preserved.


Asunto(s)
Bentonita/química , Vino/análisis , Adsorción , Calcio/química , Calcio/metabolismo , Cromatografía Líquida de Alta Presión , Cinética , Espectrometría de Masas , Ovalbúmina/química , Polifenoles/química , Riboflavina/química , Sodio/química , Sodio/metabolismo
5.
J Pharmacol Exp Ther ; 376(1): 1-11, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33087396

RESUMEN

The endocannabinoid, anandamide (AEA), stimulates cannabinoid receptors (CBRs) and is enriched in the kidney, especially the renal medulla. AEA infused into the renal outer medulla of mice stimulates urine flow rate and salt excretion. Here we show that these effects are blocked by the CBR type 1 (CB1) inverse agonist, rimonabant. Immunohistochemical analysis demonstrated the presence of CB1 in thick ascending limb (TAL) tubules. Western immunoblotting demonstrated the presence of CB1 (52 kDa) in the cortex and outer medulla of mouse kidney. The effect of direct [CP55940 (CP) or AEA] or indirect [fatty acyl amide hydrolase (FAAH) inhibitor, PF3845 (PF)] cannabinoidimetics on Na+ transport in isolated mouse TAL tubules was studied using the Na+-sensitive dye, SBFI-AM. Switching from 0 Na+ solution to control Ringer's solution (CR) rapidly increased TAL cell [Na+]i Addition of CP to CR produced a further elevation, similar in magnitude to that of ouabain, a Na+-K+-ATPase inhibitor. This [Na+]i-elevating effect of CP was time-dependent, required the presence of Na+ in the bathing solution, and was insensitive to Na+-K+-2Cl- cotransporter inhibition. Addition of PF to CR elevated [Na+]i in FAAH wild-type but not FAAH knockout (KO) TALs, whereas the additions of CP and AEA to PF-treated FAAH KO TALs increased [Na+]i An interaction between cannabinoidimetics and ouabain (Ou) was observed. Ou produced less increase in [Na+]i after cannabinoidimetic treatment, whereas cannabinoidimetics had less effect after Ou treatment. It is concluded that cannabinoidimetics, including CP and AEA, inhibit Na+ transport in TALs by inhibiting Na+ exit via Na+-K+-ATPase. SIGNIFICANCE STATEMENT: Cannabinoids including endocannabinoids induce renal urine and salt excretion and are proposed to play a physiological role in the regulation of blood pressure. Our data suggest that the mechanism of the cannabinoids involves inhibition of the sodium pump, Na+-K+-ATPase, in thick ascending limb cells and, likely, other proximal and distal tubular segments of the kidney nephron.


Asunto(s)
Antagonistas de Receptores de Cannabinoides/farmacología , Ciclohexanoles/farmacología , Diuresis , Asa de la Nefrona/metabolismo , Natriuresis , Rimonabant/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Amidohidrolasas/antagonistas & inhibidores , Amidohidrolasas/genética , Animales , Ácidos Araquidónicos/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Endocannabinoides/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ouabaína/farmacología , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Piridinas/farmacología , Sodio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores
6.
Life Sci ; 266: 118879, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33310030

RESUMEN

Acute renal injury (AKI) is a risk factor for the development of hypertension, which involves oxidative stress, changes in Na+ handling, and the intrarenal renin-angiotensin-aldosterone system (RAAS) as underlying mechanisms. We investigated in rats whether renal ischemia-reperfusion (IR) leads to changes in the proximal tubule ATP-dependent Na+ transport and the intrarenal content of RAAS components, as well as the role of NADPH oxidase. Rats weighing 300-350 g were submitted to AKI by bilateral IR (n = 25). After IR injury, the animals were followed up for 4 weeks. One part (n = 7) received daily treatment with the NADPH oxidase inhibitor apocynin (100 mg/kg, drinking water), while another part (n = 9) received apocynin 24 h before and after IR. One group was submitted to sham surgery (n = 8). Four weeks after IR, the rats presented elevated systolic blood pressure, as well as increased lipid peroxidation, NADPH oxidase activity, (Na++K+)ATPase activity, and upregulation of type 1 angiotensin II receptor in the renal cortex. On the other hand, there was a decrease in Na+-ATPase activity and downregulation of the isoforms 1 and 2 of the angiotensin-converting enzyme, type 2 angiotensin II receptor, and of the α and ε isoforms of protein kinase C. Most of these alterations was prevented by both apocynin treatment protocols. Thus, we conclude that AKI-induced by IR may induce changes in proximal tubule ATPases and RAAS components compatible with renal Na+ retention and hypertension. These data also indicate that the NADPH oxidase represents a key factor in the origin of these alterations.


Asunto(s)
Lesión Renal Aguda/complicaciones , Hipertensión/patología , Túbulos Renales Proximales/patología , NADPH Oxidasas/metabolismo , Sistema Renina-Angiotensina , Daño por Reperfusión/complicaciones , Sodio/metabolismo , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Aldosterona/metabolismo , Animales , Hipertensión/enzimología , Hipertensión/etiología , Túbulos Renales Proximales/metabolismo , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología
7.
Magn Reson Imaging ; 75: 72-88, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32979516

RESUMEN

PURPOSE: To compare three anisotropic acquisition schemes and three compressed sensing (CS) approaches for accelerated tissue sodium concentration (TSC) quantification using 23Na MRI at 7 T. MATERIALS AND METHODS: Three anisotropic 3D-radial acquisition sequences were evaluated using simulations, phantom- and in vivo TSC measurements: An anisotropic density-adapted 3D-radial sequence (3DPR-C), a 3D acquisition-weighted density-adapted stack-of-stars sampling scheme (SOS) and a SOS approach with golden-ratio rotation (SOS-GR). Eight healthy volunteers were examined at a 7 Tesla MRI system. TSC measurements of the calf were conducted with a nominal spatial resolution of Δx = (3.0 × 3.0 × 15.0) mm3 and a field of view of (156.0 × 156.0 × 240.0) mm3 for multiple undersampling factors (USF). Three CS reconstructions were evaluated: Total variation CS (TV-CS), 3D dictionary-learning compressed sensing (3D-DLCS) and TV-CS with a block matching prior (TV-BL-CS). Results of the simulations and measurements were compared to a simulated ground truth (GT) or a fully sampled reference measurement (FS), respectively. The deviation of the mean TSC evaluated in multiple ROI (mEGT/FS) and the normalized root-mean-squared error (NRMSE) for simulations were evaluated for CS and NUFFT reconstructions. RESULTS: In simulations, the SOS-GR yielded the lowest NRMSE and mEGT (< 4%) with NUFFT for an acquisition time (TA) of less than 2 min. CS further improved the results. In simulations and measurements, the best TSC quantification results were obtained with 3D-DLCS and SOS-GR (lowest NRMSE, mEGT < 2.6% in simulations, mEGT < 10.7% for phantom measurements and mEFS < 6% in vivo) with an USF = 4.1 (TA < 2 min). TV-CS showed no or only slight improvements to NUFFT. The results of TV-BL-CS were similar to 3D-DLCS. DISCUSSION: The TA for TSC measurements could be reduced to less than 2 min by using adapted sequences such as SOS-GR and CS reconstruction approaches such as 3D-DLCS or TV-BL-CS, while the quantitative accuracy stays comparable to a fully sampled NUFFT reconstruction (approx. 8 min TA). In future, the lower TA could improve clinical applicability of TSC measurements.


Asunto(s)
Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismo , Sodio/metabolismo , Adulto , Anisotropía , Humanos , Masculino , Fantasmas de Imagen , Factores de Tiempo
8.
Sheng Li Xue Bao ; 72(6): 757-764, 2020 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-33349834

RESUMEN

The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 µmol/L) and SEA0400 (1 µmol/L). The results showed that, both KB-R7943 and SEA0400 had potent negative chronotropic effects on APs of pacemaker-like cells, while such effects were only observed in some ventricular-like cardiomyocytes. The negative chronotropic effect of KB-R7943 on ventricular-like cardiomyocytes was accompanied by shortening of AP duration (APD), whereas such an effect of SEA0400 was paralleled by decrease in velocity of diastolic depolarization (Vdd). From embryonic day 9.5 (E9.5) to E10.5, the negative chronotropic effects of KB-R7943 and SEA0400 on ventricular-like APs of embryonic cardiomyocytes gradually disappeared. These results suggest that, in the short-term development of early embryo, the function of NCX may experience developmental changes as evidenced by different roles of NCX in autorhythmicity and APs generation, indicating that NCX function varies with different conditions of cardiomyocytes.


Asunto(s)
Calcio , Miocitos Cardíacos , Potenciales de Acción , Animales , Calcio/metabolismo , Ratones , Miocitos Cardíacos/metabolismo , Sodio/metabolismo , Intercambiador de Sodio-Calcio , Tiourea/farmacología
9.
Nat Commun ; 11(1): 5692, 2020 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-33173030

RESUMEN

The control of water-intake behavior is critical for life because an excessive water intake induces pathological conditions, such as hyponatremia or water intoxication. However, the brain mechanisms controlling water intake currently remain unclear. We previously reported that thirst-driving neurons (water neurons) in the subfornical organ (SFO) are cholecystokinin (CCK)-dependently suppressed by GABAergic interneurons under Na-depleted conditions. We herein show that CCK-producing excitatory neurons in the SFO stimulate the activity of GABAergic interneurons via CCK-B receptors. Fluorescence-microscopic Ca2+ imaging demonstrates two distinct subpopulations in CCK-positive neurons in the SFO, which are persistently activated under hyponatremic conditions or transiently activated in response to water drinking, respectively. Optical and chemogenetic silencings of the respective types of CCK-positive neurons both significantly increase water intake under water-repleted conditions. The present study thus reveals CCK-mediated neural mechanisms in the central nervous system for the control of water-intake behaviors.


Asunto(s)
Conducta de Ingestión de Líquido/fisiología , Neuronas/fisiología , Órgano Subfornical/citología , Animales , Masculino , Ratones , Microscopía Fluorescente/métodos , Sodio/metabolismo , Órgano Subfornical/fisiología
10.
Chemosphere ; 261: 128051, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33113650

RESUMEN

The potential toxicity of copper nanoparticles (CuNPs) to early stages of fishes is not fully understood, and little is known about their effects on ionocytes and associated functions. This study used zebrafish embryos as a model to investigate the toxic effects of CuNPs on two subtypes of ionocytes. Zebrafish embryos were exposed to 0.1, 1, and 3 mg L-1 CuNPs for 96 h. After exposure, whole-body Na+ and Ca2+ contents were significantly reduced at ≥0.1 mg L-1, while the K+ content had decreased at ≥1 mg L-1. H+ and NH4+ excretion by the skin significantly decreased at ≥1 mg L-1. The number of living ionocytes labeled with rhodamine-123 had significantly decreased with ≥0.1 mg L-1 CuNPs. The ionocyte subtypes of H+-ATPase-rich (HR) and Na+/K+-ATPase-rich (NaR) cells were labeled by immunostaining and had decreased with ≥1 mg L-1. Shrinkage of the apical opening of ionocytes was revealed by scanning electronic microscopy. Functional impairment was also reflected by changes in gene expressions, including ion transporters/channels and Ca2+-regulatory hormones. This study shows that CuNP exposure can impair two subtypes of ionocytes and their associated functions, including Na+/Ca2+ uptake and H+/NH4+ excretion in zebrafish embryos.


Asunto(s)
Amoníaco/metabolismo , Cobre/toxicidad , Embrión no Mamífero/efectos de los fármacos , Nanopartículas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/metabolismo , Ácidos/metabolismo , Animales , Transporte Biológico , Calcio/metabolismo , Cobre/metabolismo , Embrión no Mamífero/metabolismo , Canales Iónicos/metabolismo , Iones/metabolismo , Nanopartículas/metabolismo , Piel/metabolismo , Sodio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Contaminantes Químicos del Agua/metabolismo , Proteínas de Pez Cebra/metabolismo
11.
Ecotoxicol Environ Saf ; 206: 111358, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33007539

RESUMEN

Rice (Oryza sativa L.) productivity is greatly affected by soil salinity and melatonin (MLT) has long been recognized as a positive molecule that can alleviate the damage caused by salt. Here, the role of nitric oxide (NO) in the regulation of salt tolerance by MLT was investigated in rice. MLT pretreatment increased the fresh and dry weight of rice seedlings under salt stress. Its beneficial effects include less relative electrolyte leakage (REL) and better K+/Na+ homeostasis. MLT increased the activity of nitric oxide synthase (NOS). The polyamines (PAs) content and the utilization of arginine were also increased, thereby increasing NO content in salt-stressed rice seedlings. Pharmacological approach showed that NO, as a necessary downstream signaling molecule, was involved in the regulation of MLT on the K+/Na+ homeostasis of rice. Under salt stress, MLT improved the H+-pumps activities in plasma membrane (PM) and vacuole membrane (VM) in roots, MLT also increased the ATP content of rice roots by increasing the NO content of rice. Thus, the efflux of Na+ and the influx of K+ were promoted. When endogenous NO was scavenged, the regulation of K+/Na+ homeostasis by MLT was blocked. Therefore, MLT mediated K+/Na+ homeostasis of rice under salt stress by mediating NO.


Asunto(s)
Homeostasis/fisiología , Melatonina/metabolismo , Óxido Nítrico/metabolismo , Oryza/fisiología , Potasio/metabolismo , Estrés Salino/fisiología , Sodio/metabolismo , Iones/metabolismo , Oryza/metabolismo , Raíces de Plantas/efectos de los fármacos , Salinidad , Tolerancia a la Sal , Plantones/efectos de los fármacos
12.
Nat Commun ; 11(1): 4368, 2020 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-32868758

RESUMEN

Increased extracellular sodium activates Th17 cells, which provide protection from bacterial and fungal infections. Whilst high salt diets have been shown to worsen autoimmune disease, the immunological consequences of clinical salt depletion are unknown. Here, we investigate immunity in patients with inherited salt-losing tubulopathies (SLT). Forty-seven genotyped SLT patients (with Bartter, Gitelman or EAST Syndromes) are recruited. Clinical features of dysregulated immunity are recorded with a standardised questionnaire and immunological investigations of IL-17 responsiveness undertaken. The effects of altering extracellular ionic concentrations on immune responses are then assessed. Patients are hypokalaemic and hypomagnesaemic, with reduced interstitial sodium stores determined by 23Na-magnetic resonance imaging. SLT patients report increased mucosal infections and allergic disease compared to age-matched controls. Aligned with their clinical phenotype, SLT patients have an increased ratio of Th2:Th17 cells. SLT Th17 and Tc17 polarisation is reduced in vitro, yet STAT1 and STAT3 phosphorylation and calcium flux following T cell activation are unaffected. In control cells, the addition of extracellular sodium (+40 mM), potassium (+2 mM), or magnesium (+1 mM) reduces Th2:Th17 ratio and augments Th17 polarisation. Our results thus show that the ionic environment typical in SLT impairs IL-17 immunity, but the intracellular pathways that mediate salt-driven Th17 polarisation are intact and in vitro IL-17 responses can be reinvigorated by increasing extracellular sodium concentration. Whether better correction of extracellular ions can rescue the immunophenotype in vivo in SLT patients remains unknown.


Asunto(s)
Síndromes de Inmunodeficiencia/etiología , Interleucina-17/metabolismo , Túbulos Renales Distales/patología , Adolescente , Adulto , Anciano de 80 o más Años , Animales , Preescolar , Enfermedad Crónica , Estudios de Cohortes , Femenino , Enfermedades Genéticas Congénitas , Humanos , Magnesio/metabolismo , Masculino , Persona de Mediana Edad , Potasio/metabolismo , Sales (Química)/metabolismo , Sales (Química)/uso terapéutico , Sodio/metabolismo , Cloruro de Sodio/metabolismo , Cloruro de Sodio Dietético/uso terapéutico , Células Th17/metabolismo , Células Th2/metabolismo , Adulto Joven
13.
PLoS Biol ; 18(9): e3000873, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32966273

RESUMEN

The inhibitory axonless olfactory bulb granule cells form reciprocal dendrodendritic synapses with mitral and tufted cells via large spines, mediating recurrent and lateral inhibition. As a case in point for dendritic transmitter release, rat granule cell dendrites are highly excitable, featuring local Na+ spine spikes and global Ca2+- and Na+-spikes. To investigate the transition from local to global signaling, we performed holographic, simultaneous 2-photon uncaging of glutamate at up to 12 granule cell spines, along with whole-cell recording and dendritic 2-photon Ca2+ imaging in acute juvenile rat brain slices. Coactivation of less than 10 reciprocal spines was sufficient to generate diverse regenerative signals that included regional dendritic Ca2+-spikes and dendritic Na+-spikes (D-spikes). Global Na+-spikes could be triggered in one third of granule cells. Individual spines and dendritic segments sensed the respective signal transitions as increments in Ca2+ entry. Dendritic integration as monitored by the somatic membrane potential was mostly linear until a threshold number of spines was activated, at which often D-spikes along with supralinear summation set in. As to the mechanisms supporting active integration, NMDA receptors (NMDARs) strongly contributed to all aspects of supralinearity, followed by dendritic voltage-gated Na+- and Ca2+-channels, whereas local Na+ spine spikes, as well as morphological variables, barely mattered. Because of the low numbers of coactive spines required to trigger dendritic Ca2+ signals and thus possibly lateral release of GABA onto mitral and tufted cells, we predict that thresholds for granule cell-mediated bulbar lateral inhibition are low. Moreover, D-spikes could provide a plausible substrate for granule cell-mediated gamma oscillations.


Asunto(s)
Potenciales de Acción , Señalización del Calcio , Dendritas/metabolismo , Bulbo Olfatorio/metabolismo , Sodio/metabolismo , Animales , Calcio/metabolismo , Femenino , Holografía , Técnicas In Vitro , Masculino , Ratas Wistar , Receptores de N-Metil-D-Aspartato/metabolismo
14.
PLoS One ; 15(9): e0238447, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32881909

RESUMEN

BACKGROUND: Polyamines are involved in a wide variety of biological processes including a marked effect on the structure and function of DNA. During our study on the interaction of polyamines with DNA, we found that K+ enhanced in vitro gene expression in the presence of polyamine more strongly than Na+. Thus, we sought to clarify the physico-chemical mechanism underlying this marked difference between the effects of K+ and Na+. PRINCIPAL FINDINGS: It was found that K+ enhanced gene expression in the presence of spermidine, SPD(3+), much more strongly than Na+, through in vitro experiments with a Luciferase assay on cell extracts. Single-DNA observation by fluorescence microscopy showed that Na+ prevents the folding transition of DNA into a compact state more strongly than K+. 1H NMR measurement revealed that Na+ inhibits the binding of SPD to DNA more strongly than K+. Thus, SPD binds to DNA more favorably in K+-rich medium than in Na+-rich medium, which leads to favorable conditions for RNA polymerase to access DNA by decreasing the negative charge. CONCLUSION AND SIGNIFICANCE: We found that Na+ and K+ exhibit markedly different effects through competitive binding with a cationic polyamine, SPD, to DNA, which causes a large difference in the higher-order structure of genomic DNA. It is concluded that the larger favorable effect of Na+ than K+ on in vitro gene expression observed in this study is well attributable to the significant difference between Na+ and K+ on the competitive binding inducing conformational transition of DNA.


Asunto(s)
Expresión Génica/efectos de los fármacos , Potasio/metabolismo , Sodio/metabolismo , Fenómenos Bioquímicos , ADN/metabolismo , Poliaminas/metabolismo , Poliaminas/farmacología , Espermidina/farmacología , Espermina/farmacología
15.
Am J Physiol Regul Integr Comp Physiol ; 319(4): R412-R427, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32755465

RESUMEN

In zebrafish (Danio rerio), a specific ionocyte subtype, the H+-ATPase-rich (HR) cell, is presumed to be a significant site of transepithelial Na+ uptake/acid secretion. During acclimation to environments differing in ionic composition or pH, ionic and acid-base regulations are achieved by adjustments to the activity level of HR cell ion transport proteins. In previous studies, the quantitative assessment of mRNA levels for genes involved in ionic and acid-base regulations relied on measurements using homogenates derived from the whole body (larvae) or the gill (adult). Such studies cannot distinguish whether any differences in gene expression arise from adjustments of ionocyte subtype numbers or transcriptional regulation specifically within individual ionocytes. The goal of the present study was to use fluorescence-activated cell sorting to separate the HR cells from other cellular subpopulations to facilitate the measurement of gene expression of HR cell-specific transporters and enzymes from larvae exposed to low pH (pH 4.0) or low Na+ (5 µM) conditions. The data demonstrate that treatment of larvae with acidic water for 4 days postfertilization caused cell-specific increases in H+-ATPase (atp6v1aa), ca17a, ca15a, nhe3b, and rhcgb mRNA in addition to increases in mRNA linked to cell proliferation. In fish exposed to low Na+, expression of nhe3b and rhcgb was increased owing to HR cell-specific regulation and elevated numbers of HR cells. Thus, the results of this study demonstrate that acclimation to low pH or low Na+ environmental conditions is facilitated by HR cell-specific transcriptional control and by HR cell proliferation.


Asunto(s)
Transporte Iónico/genética , ATPasas de Translocación de Protón/genética , Intercambiadores de Sodio-Hidrógeno/genética , Agua , Proteínas de Pez Cebra/genética , Animales , Branquias/metabolismo , Concentración de Iones de Hidrógeno , ATPasas de Translocación de Protón/metabolismo , Sodio/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Pez Cebra , Proteínas de Pez Cebra/metabolismo
16.
Am J Physiol Renal Physiol ; 319(3): F487-F505, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32744084

RESUMEN

Each day, ~1.7 kg of NaCl and 180 liters of water are reabsorbed by nephron segments in humans, with urinary excretion fine tuned to meet homeostatic requirements. These tasks are coordinated by a spectrum of renal Na+ transporters and channels. The goal of the present study was to investigate the extent to which inhibitors of transepithelial Na+ transport (TNa) along the nephron alter urinary solute excretion and how those effects may vary between male and female subjects. To accomplish that goal, we developed sex-specific multinephron models that represent detailed transcellular and paracellular transport processes along the nephrons of male and female rat kidneys. We simulated inhibition of Na+/H+ exchanger 3 (NHE3), bumetanide-sensitive Na+-K+-2Cl- cotransporter (NKCC2), Na+-Cl- cotransporter (NCC), and amiloride-sensitive epithelial Na+ channel (ENaC). NHE3 inhibition simulations predicted a substantially reduced proximal tubule TNa, and NKCC2 inhibition substantially reduced thick ascending limb TNa. Both gave rise to diuresis, natriuresis, and kaliuresis, with those effects stronger in female rats. While NCC inhibition was predicted to have only minor impact on renal TNa, it nonetheless had a notable effect of enhancing excretion of Na+, K+, and Cl-, particularly in female rats. Inhibition of ENaC was predicted to have opposite effects on the excretion of Na+ (increased) and K+ (decreased) and to have only a minor impact on whole kidney TNa. Unlike inhibition of other transporters, ENaC inhibition induced stronger natriuresis and diuresis in male rats than female rats. Overall, model predictions agreed well with measured changes in Na+ and K+ excretion in response to diuretics and Na+ transporter mutations.


Asunto(s)
Simulación por Computador , Modelos Biológicos , Nefronas/fisiología , Simportadores de Cloruro de Sodio-Potasio/metabolismo , Sodio/metabolismo , Animales , Transporte Biológico , Femenino , Masculino , Ratas , Factores Sexuales , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico
17.
Rev Med Suisse ; 16(701): 1450-1455, 2020 Aug 05.
Artículo en Francés | MEDLINE | ID: mdl-32833367

RESUMEN

The Covid 19 pandemic remains a serious public health problem until effective drugs and/or vaccines are available. Can we explain why so many people remain asymptomatic but nevertheless highly contagious explaining the speed with which the pandemic has spread around the world? Can we explain why the acute respiratory distress syndrome (ARDS) appears late but can so quickly have a fatal outcome? In the lung, mucociliary clearance (CMC) and alveolar clearance (CA) depend on the transport of sodium through the plasma membrane of epithelial cells. This transport is mediated by a highly selective sodium channel (Epithelial Sodium Channel = ENaC) which could be a key element in the pulmonary pathophysiology of SARS-CoV-2 infection.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/metabolismo , Modelos Biológicos , Neumonía Viral/metabolismo , Sodio/metabolismo , Infecciones por Coronavirus/virología , Humanos , Transporte Iónico , Pandemias , Neumonía Viral/virología
18.
Nat Commun ; 11(1): 4337, 2020 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-32859897

RESUMEN

Intracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodelling occurs. Here, we assess whether acute (75 µM ouabain 100 nM blebbistatin) or chronic myocardial Nai load (PLM3SA mouse) are causally linked to metabolic remodelling and whether the failing heart shares a common Na-mediated metabolic 'fingerprint'. Control (PLMWT), transgenic (PLM3SA), ouabain-treated and hypertrophied Langendorff-perfused mouse hearts are studied by 23Na, 31P, 13C NMR followed by 1H-NMR metabolomic profiling. Elevated Nai leads to common adaptive metabolic alterations preceding energetic impairment: a switch from fatty acid to carbohydrate metabolism and changes in steady-state metabolite concentrations (glycolytic, anaplerotic, Krebs cycle intermediates). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 ameliorates the metabolic changes. In silico modelling indicates altered metabolic fluxes (Krebs cycle, fatty acid, carbohydrate, amino acid metabolism). Prevention of Nai overload or inhibition of Na/Camito may be a new approach to ameliorate metabolic dysregulation in heart failure.


Asunto(s)
Reprogramación Celular/fisiología , Citoplasma/metabolismo , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Sodio/metabolismo , Animales , Modelos Animales de Enfermedad , Metabolismo Energético , Técnicas de Sustitución del Gen , Corazón , Hipertrofia , Preparación de Corazón Aislado , Masculino , Enfermedades Metabólicas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratas , Ratas Wistar , Sodio/sangre , Intercambiador de Sodio-Calcio/efectos de los fármacos , Tiazepinas/farmacología
19.
Nat Commun ; 11(1): 4222, 2020 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-32839436

RESUMEN

Our understanding of Na+ homeostasis has recently been reshaped by the notion of skin as a depot for Na+ accumulation in multiple cardiovascular diseases and risk factors. The proposed water-independent nature of tissue Na+ could induce local pathogenic changes, but lacks firm demonstration. Here, we show that tissue Na+ excess upon high Na+ intake is a systemic, rather than skin-specific, phenomenon reflecting architectural changes, i.e. a shift in the extracellular-to-intracellular compartments, due to a reduction of the intracellular or accumulation of water-paralleled Na+ in the extracellular space. We also demonstrate that this accumulation is unlikely to justify the observed development of experimental hypertension if it were water-independent. Finally, we show that this isotonic skin Na+ excess, reflecting subclinical oedema, occurs in hypertensive patients and in association with aging. The implications of our findings, questioning previous assumptions but also reinforcing the importance of tissue Na+ excess, are both mechanistic and clinical.


Asunto(s)
Edema/metabolismo , Homeostasis/fisiología , Sodio/metabolismo , Equilibrio Hidroelectrolítico/fisiología , Envejecimiento/metabolismo , Animales , Edema/diagnóstico , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Miocardio/metabolismo , Especificidad de Órganos , Concentración Osmolar , Potasio/metabolismo , Ratas Endogámicas WKY , Piel/metabolismo , Factores de Transcripción/metabolismo
20.
PLoS One ; 15(8): e0237347, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32785272

RESUMEN

Here we examine a class of neurons that have been recently explored, the somatosensory neuronal subclass of cold thermosensors. We create a mathematical model of a cold sensing neuron that has been formulated to understand the variety of ionic channels involved. In particular this model showcases the role of TRPM8 and voltage gated potassium channels in setting the temperature dependent activation and inactivation threshold level. Bifurcation analysis of the model demonstrates that a Hodgkin-Huxley type model with additional TRPM8 channels is sufficient to replicate observable experimental features of when different threshold level cold thermosensors turn on. Additionally, our analysis gives insight into what is happening at the temperature levels at which these neurons shut off and the role sodium and leak currents may have in this. This type of model construction and analysis provides a framework moving forward that will help tackle less well understood neuronal classes and their important ionic channels.


Asunto(s)
Frío , Modelos Neurológicos , Canales Catiónicos TRPM/metabolismo , Termorreceptores/fisiología , Sensación Térmica/fisiología , Animales , Potenciales de la Membrana/fisiología , Potasio/metabolismo , Sodio/metabolismo
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