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Pflugers Archiv : European Journal of... Feb 2022The capacity of astrocytes to adapt their biochemical and functional features upon physiological and pathological stimuli is a fundamental property at the basis of their...
The capacity of astrocytes to adapt their biochemical and functional features upon physiological and pathological stimuli is a fundamental property at the basis of their ability to regulate the homeostasis of the central nervous system (CNS). It is well known that in primary cultured astrocytes, the expression of plasma membrane ion channels and transporters involved in homeostatic tasks does not closely reflect the pattern observed in vivo. The individuation of culture conditions that promote the expression of the ion channel array found in vivo is crucial when aiming at investigating the mechanisms underlying their dynamics upon various physiological and pathological stimuli. A chemically defined medium containing growth factors and hormones (G5) was previously shown to induce the growth, differentiation, and maturation of primary cultured astrocytes. Here we report that under these culture conditions, rat cortical astrocytes undergo robust morphological changes acquiring a multi-branched phenotype, which develops gradually during the 2-week period of culturing. The shape changes were paralleled by variations in passive membrane properties and background conductance owing to the differential temporal development of inwardly rectifying chloride (Cl) and potassium (K) currents. Confocal and immunoblot analyses showed that morphologically differentiated astrocytes displayed a large increase in the expression of the inward rectifier Cl and K channels ClC-2 and Kir4.1, respectively, which are relevant ion channels in vivo. Finally, they exhibited a large diminution of the intermediate filaments glial fibrillary acidic protein (GFAP) and vimentin which are upregulated in reactive astrocytes in vivo. Taken together the data indicate that long-term culturing of cortical astrocytes in this chemical-defined medium promotes a quiescent functional phenotype. This culture model could aid to address the regulation of ion channel expression involved in CNS homeostasis in response to physiological and pathological challenges.
Topics: Animals; Astrocytes; CLC-2 Chloride Channels; Cell Membrane; Central Nervous System; Chlorides; Homeostasis; Patch-Clamp Techniques; Potassium; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley; Vimentin
PubMed: 34734327
DOI: 10.1007/s00424-021-02627-x -
Poultry Science Jul 2019Broiler dietary potassium (K) and available phosphorous (AvP) have decreased in recent years but both ions are intimately involved in the elimination of hydrogen ions...
Broiler dietary potassium (K) and available phosphorous (AvP) have decreased in recent years but both ions are intimately involved in the elimination of hydrogen ions that are produced during rapid growth. It was hypothesized that the decrease of these dietary electrolytes was related to the development of myopathies, and thus increased dietary K and/or AvP would reduce the occurrence of breast myopathies. A total of 320 Ross male broiler chicks were placed into 16 pens and fed 2 diet series containing either decreasing AvP levels of 0.45, 0.40, and 0.35% in the starter, grower, and finisher diets, respectively (Decline), or a fixed AvP of 0.45% in all dietary phases (Fixed). To complete a 2 × 2 design either normal basal dietary K (K-) (0.86, 0.77, 0.68%) or added dietary K (K+) (1.01, 0.93, 0.88%) were also applied to starter, grower, and finisher diets, respectively. Blood physiology was measured at 29 and 42 d. Carcass data, wooden breast and white striping scores were measured at 35 and 43 d. The K+ diets improved feed conversion ratio at 35 d (1.52 vs 1.57 g: g), reduced body weight at 42 d (3524 vs 3584 g), reduced hemoglobin (6.83 vs 7.58 g/dL), and packed cell volume (20.1 vs 22.3%) at 29 d, reduced ionized blood calcium (1.42 vs 1.47 mmol/L) at 42 d, and reduced partial pressure of blood CO2 (49.1 vs 54.7 mm/Hg) at 42 d relative to broilers fed basal K- diets (P < 0.05). Fixed AvP diets improved feed conversion ratio at 28 and 42 d, increased percentage breast meat (28.85 vs 27.58%) and carcass water pickup (2.72 vs 1.42%) at 35 d, and reduced wooden breast (2.88 vs 3.69) at 43 d (P < 0.05).
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Chickens; Diet; Male; Muscular Diseases; Pectoralis Muscles; Phosphorus; Potassium, Dietary; Poultry Diseases
PubMed: 30690518
DOI: 10.3382/ps/pez015 -
Metal Ions in Life Sciences 2016The two alkali cations Na(+) and K(+) have similar relative abundances in the earth crust but display very different distributions in the biosphere. In all living...
The two alkali cations Na(+) and K(+) have similar relative abundances in the earth crust but display very different distributions in the biosphere. In all living organisms, K(+) is the major inorganic cation in the cytoplasm, where its concentration (ca. 0.1 M) is usually several times higher than that of Na(+). Accumulation of Na(+) at high concentrations in the cytoplasm results in deleterious effects on cell metabolism, e.g., on photosynthetic activity in plants. Thus, Na(+) is compartmentalized outside the cytoplasm. In plants, it can be accumulated at high concentrations in vacuoles, where it is used as osmoticum. Na(+) is not an essential element in most plants, except in some halophytes. On the other hand, it can be a beneficial element, by replacing K(+) as vacuolar osmoticum for instance. In contrast, K(+) is an essential element. It is involved in electrical neutralization of inorganic and organic anions and macromolecules, pH homeostasis, control of membrane electrical potential, and the regulation of cell osmotic pressure. Through the latter function in plants, it plays a role in turgor-driven cell and organ movements. It is also involved in the activation of enzymes, protein synthesis, cell metabolism, and photosynthesis. Thus, plant growth requires large quantities of K(+) ions that are taken up by roots from the soil solution, and then distributed throughout the plant. The availability of K(+) ions in the soil solution, slowly released by soil particles and clays, is often limiting for optimal growth in most natural ecosystems. In contrast, due to natural salinity or irrigation with poor quality water, detrimental Na(+) concentrations, toxic for all crop species, are present in many soils, representing 6 % to 10 % of the earth's land area. Three families of ion channels (Shaker, TPK/KCO, and TPC) and 3 families of transporters (HAK, HKT, and CPA) have been identified so far as contributing to K(+) and Na(+) transport across the plasmalemma and internal membranes, with high or low ionic selectivity. In the model plant Arabidopsis thaliana, these families gather at least 70 members. Coordination of the activities of these systems, at the cell and whole plant levels, ensures plant K(+) nutrition, use of Na(+) as a beneficial element, and adaptation to saline conditions.
Topics: Carrier Proteins; Cations; Gene Expression Regulation, Plant; Homeostasis; Ion Channels; Plant Proteins; Plants; Potassium; Sodium; Soil; Water
PubMed: 26860305
DOI: 10.1007/978-3-319-21756-7_9 -
International Journal of Molecular... Nov 2023Ternary glassy electrolytes containing KS as a glass modifier and PS as a network former are synthesized by introducing a new type of complex and asymmetric salt,...
Ternary glassy electrolytes containing KS as a glass modifier and PS as a network former are synthesized by introducing a new type of complex and asymmetric salt, potassium triflate (KOTf), to obtain unprecedented K ion conductivity at ambient temperature. The glasses are synthesized using a conventional quenching technique at a low temperature. In general, alkali ionic glassy electrolytes of ternary systems, specifically for Li and Na ion conductivity, have been studied with the addition of halide salts or oxysalts such as MSO, MSiO, MPO (M = Li or Na), etc. We introduce a distinct and complex salt, potassium triflate (KOTf) with asymmetric anion, to the conventional glass modifier and former to synthesize K-ion-conducting glassy electrolytes. Two series of glassy electrolytes with a ternary system of (0.9-x)KS-xPS-0.1KOTf (x = 0.15, 0.30, 0.45, 0.60, and 0.75) and z(KS-2PS)-yKOTf (y = 0.05, 0.10, 0.15, 0.20, and 0.25) on a straight line of z(KS-2PS) are studied for their K ionic conductivities by using electrochemical impedance spectroscopy (EIS). The composition 0.3KS-0.6PS-0.1KOTf is found to have the highest conductivity among the studied glassy electrolytes at ambient temperature with the value of 1.06 × 10 S cm, which is the highest of all pure K-ion-conducting glasses reported to date. Since the glass transition temperatures of the glasses are near 100 °C, as demonstrated by DSC, temperature-dependent conductivities are studied within the range of 25 to 100 °C to determine the activation energies. A Raman spectroscopic study shows the variation in the structural units PS43-, P2S74-, and P2S64- of the network former for different glassy electrolytes. It seems that there is a role of P2S74- and P2S64- in K-ion conductivity in the glassy electrolytes because the spectroscopic results are compatible with the composition-dependent, room-temperature conductivity trend.
Topics: Electrolytes; Ions; Phosphates; Potassium; Sodium Chloride; Sodium Chloride, Dietary
PubMed: 38069182
DOI: 10.3390/ijms242316855 -
American Journal of Physiology. Cell... Sep 2022Channel proteins are vital for conducting ions throughout the body and are especially relevant to retina physiology. Inward rectifier potassium (Kir) channels are a... (Review)
Review
Channel proteins are vital for conducting ions throughout the body and are especially relevant to retina physiology. Inward rectifier potassium (Kir) channels are a class of K channels responsible for maintaining membrane potential and extracellular K concentrations. Studies of the gene (that encodes Kir protein) expression identified the presence of all of the subclasses (Kir 1-7) of Kir channels in the retina or retinal-pigmented epithelium (RPE). However, functional studies have established the involvement of the Kir4.1 homotetramer and Kir4.1/5.1 heterotetramer in Müller glial cells, Kir2.1 in bipolar cells, and Kir7.1 in the RPE cell physiology. Here, we propose the potential roles of Kir channels in the retina based on the physiological contributions to the brain, pancreatic, and cardiac tissue functions. There are several open questions regarding the expressed genes in the retina and RPE. For example, why does not the Kir channel subtype gene expression correspond with protein expression? Catching up with multiomics or functional "omics" approaches might shed light on posttranscriptional changes that might influence Kir subunit mRNA translation within the retina that guides our vision.
Topics: Ions; Potassium; Potassium Channels, Inwardly Rectifying; RNA, Messenger; Retina
PubMed: 35912989
DOI: 10.1152/ajpcell.00112.2022 -
Journal of Experimental & Clinical... Sep 2023Malignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis....
BACKGROUND
Malignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis. Due to its complex composition of cellular and acellular components malignant ascites creates a unique tumor microenvironment, which mediates immunosuppression and promotes progression of disease. However, the immunosuppressive mechanisms remain poorly understood.
METHODS
In the present study, we explored the antitumor activity of healthy donor NK and T cells directed against ovarian cancer cells in presence of malignant ascites derived from patients with advanced or recurrent peritoneal carcinomatosis. A wide range of methods was used to study the effect of ascites on NK and T cells (FACS, ELISA, EliSpot, qPCR, Live-cell and confocal microscopy, Western blot and electrolyte flux assays). The ascites components were assessed using quantitative analysis (nephelometry, potentiometry and clinical chemistry) and separation methods (dialysis, ultracentrifugal filtration and lipid depletion).
RESULTS
Ascites rapidly inhibited NK cell degranulation, tumor lysis, cytokine secretion and calcium signaling. Similarly, target independent NK and T cell activation was impaired in ascites environment. We identified imbalanced electrolytes in ascites as crucial factors causing extensive immunosuppression of NK and T cells. Specifically, high sodium, low chloride and low potassium content significantly suppressed NK-mediated cytotoxicity. Electrolyte imbalance led to changes in transcription and protein expression of electrolyte channels and impaired NK and T cell activation. Selected inhibitors of sodium electrolyte channels restored intracellular calcium flux, conjugation, degranulation and transcript expression of signaling molecules. The levels of ascites-mediated immunosuppression and sodium/chloride/potassium imbalance correlated with poor patient outcome and selected molecular alterations were confirmed in immune cells from ovarian cancer patients.
CONCLUSION
Our data suggest a novel electrolyte-based mechanism of immunosuppression in malignant ascites of patients with peritoneal carcinomatosis. We show for the first time that the immunosuppression of NK cytotoxicity in coculture assays is correlated to patient poor survival. Therapeutic application of sodium channel inhibitors may provide new means for restoring immune cell activity in ascites or similar electrolyte imbalanced environments.
Topics: Humans; Female; Peritoneal Neoplasms; Ascites; Chlorides; T-Lymphocytes; Ovarian Neoplasms; Potassium; Tumor Microenvironment
PubMed: 37684704
DOI: 10.1186/s13046-023-02798-8 -
Nutrients Jul 2023Higher salt (sodium) intake has been associated with higher blood pressure (BP). The degree of association may be influenced by factors such as age, origin, and dietary...
Higher salt (sodium) intake has been associated with higher blood pressure (BP). The degree of association may be influenced by factors such as age, origin, and dietary components. This study aimed to evaluate the 24 h urinary sodium (Na) and potassium (K) excretion in normotensive and hypertensive Dominican adults and estimate their salt intake. 163 volunteers (18-80 years old) participated in a cross-sectional study. The 24 h Na and K urinary excretion were measured using an ion-selective electrode technique. Na and K urinary excretion (99.4 ± 46.5 and 35.0 ± 17.5 mmol/24 h) did not correlate with BP, except in the normotensive group, in which K correlated with SBP (0.249, = 0.019). Na and K excretion were similar in normotensive and hypertensive subjects. When considering two age groups (18-45, 46-80 years), the Na-to-K molar ratio (3.1 ± 1.3) was higher in younger subjects ( = 0.040). Na-to-K ratio was associated with DBP in the total group (r = 0.153, = 0.052), in the hypertensive group (r = 0.395, < 0.001), and in the older group with SBP (0.350, = 0.002) and DBP (0.373, < 0.001). In the older group, Na-to-K ratio and DBP correlated after controlling for subjects with hypertension controlled by treatment (r = 0.236, = 0.041). The Na-to-K ratio correlated, when salt intake was over 5 g/day (52.2%), with SBP (rho = 0.219, = 0.044) and DBP (rho = 0.259, = 0.017). Determinants of BP in the total sample were age (SBP, beta: 0.6 ± 0.1, < 0.001; DBP, beta: 0.2 ± 0.1, < 0.002), sex (SBP, beta: 11.2 ± 3.5, 0.001), body mass index (BMI) (SBP, beta: 1.0 ± 0.3, < 0.001; DBP, beta: 0.4 ± 0.2, = 0.01), and Na-to-K ratio (SBP, beta: 3.0 ± 1.1, = 0.008; DBP, beta: -12.3 ± 4.0, = 0.002). Sex and BMI were determinants in the younger group. Na-to-K molar ratio was determinant in the older group (SBP, beta: 6.7 ± 2.4, 0.005; DBP, beta: 3.8 ± 1.1, < 0.001). The mean Na and salt intakes (2.3 and 5.8 g/day) were slightly higher and the K intake lower (1.4 g/day) than WHO recommendations.
Topics: Humans; Adult; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Blood Pressure; Potassium; Sodium Chloride, Dietary; Cross-Sectional Studies; Dominican Republic; Hypertension; Sodium; Sodium, Dietary
PubMed: 37513615
DOI: 10.3390/nu15143197 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2023Virtually 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... (Review)
Review
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.
Topics: Humans; Bartter Syndrome; Pseudohypoaldosteronism; Potassium; Aldosterone; Hypokalemia; Gitelman Syndrome; Hyperkalemia; Clinical Relevance; Epithelial Sodium Channels; Kidney Tubules, Distal; Sodium; Hypertension; Alkalosis; Water; Kidney
PubMed: 37089096
DOI: No ID Found -
Analytical and Bioanalytical Chemistry Jan 2021Annotation and interpretation of full scan electrospray mass spectra of metabolites is complicated by the presence of a wide variety of ions. Not only protonated,...
Annotation and interpretation of full scan electrospray mass spectra of metabolites is complicated by the presence of a wide variety of ions. Not only protonated, deprotonated, and neutral loss ions but also sodium, potassium, and ammonium adducts as well as oligomers are frequently observed. This diversity challenges automatic annotation and is often poorly addressed by current annotation tools. In many cases, annotation is integrated in metabolomics workflows and is based on specific chromatographic peak-picking tools. We introduce mzAdan, a nonchromatography-based multipurpose standalone application that was developed for the annotation and exploration of convolved high-resolution ESI-MS spectra. The tool annotates single or multiple accurate mass spectra using a customizable adduct annotation list and outputs a list of [M+H] candidates. MzAdan was first tested with a collection of 408 analytes acquired with flow injection analysis. This resulted in 402 correct [M+H] identifications and, with combinations of sodium, ammonium, and potassium adducts and water and ammonia losses within a tolerance of 10 mmu, explained close to 50% of the total ion current. False positives were monitored with mass accuracy and bias as well as chromatographic behavior which led to the identification of adducts with calcium instead of the expected potassium. MzAdan was then integrated in a workflow with XCMS for the untargeted LC-MS data analysis of a 52 metabolite standard mix and a human urine sample. The results were benchmarked against three other annotation tools, CAMERA, findMAIN, and CliqueMS: findMAIN and mzAdan consistently produced higher numbers of [M+H] candidates compared with CliqueMS and CAMERA, especially with co-eluting metabolites. Detection of low-intensity ions and correct grouping were found to be essential for annotation performance. Graphical abstract.
Topics: Algorithms; Calcium; Chromatography, Liquid; Databases, Factual; False Positive Reactions; Flow Injection Analysis; Humans; Ions; Mass Spectrometry; Metabolomics; Pattern Recognition, Automated; Potassium; Software; Urinalysis
PubMed: 33123762
DOI: 10.1007/s00216-020-03019-3 -
Cellular and Molecular Life Sciences :... Nov 2014The function and survival of pancreatic β cells critically rely on complex electrical signaling systems composed of a series of ionic events, namely fluxes of K(+),... (Review)
Review
The function and survival of pancreatic β cells critically rely on complex electrical signaling systems composed of a series of ionic events, namely fluxes of K(+), Na(+), Ca(2+) and Cl(-) across the β cell membranes. These electrical signaling systems not only sense events occurring in the extracellular space and intracellular milieu of pancreatic islet cells, but also control different β cell activities, most notably glucose-stimulated insulin secretion. Three major ion fluxes including K(+) efflux through ATP-sensitive K(+) (KATP) channels, the voltage-gated Ca(2+) (CaV) channel-mediated Ca(2+) influx and K(+) efflux through voltage-gated K(+) (KV) channels operate in the β cell. These ion fluxes set the resting membrane potential and the shape, rate and pattern of firing of action potentials under different metabolic conditions. The KATP channel-mediated K(+) efflux determines the resting membrane potential and keeps the excitability of the β cell at low levels. Ca(2+) influx through CaV1 channels, a major type of β cell CaV channels, causes the upstroke or depolarization phase of the action potential and regulates a wide range of β cell functions including the most elementary β cell function, insulin secretion. K(+) efflux mediated by KV2.1 delayed rectifier K(+) channels, a predominant form of β cell KV channels, brings about the downstroke or repolarization phase of the action potential, which acts as a brake for insulin secretion owing to shutting down the CaV channel-mediated Ca(2+) entry. These three ion channel-mediated ion fluxes are the most important ionic events in β cell signaling. This review concisely discusses various ionic mechanisms in β cell signaling and highlights KATP channel-, CaV1 channel- and KV2.1 channel-mediated ion fluxes.
Topics: Action Potentials; Adenosine Triphosphate; Animals; Calcium; Calcium Channels; Cell Membrane; Exocytosis; Humans; Insulin; Insulin-Secreting Cells; Ions; Membrane Potentials; Potassium; Potassium Channels; Signal Transduction
PubMed: 25052376
DOI: 10.1007/s00018-014-1680-6