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The Journal of Biological Chemistry Sep 2016Regulation of enzymes through metal ion complexation is widespread in biology and underscores a physiological need for stability and high catalytic activity that likely... (Review)
Review
Regulation of enzymes through metal ion complexation is widespread in biology and underscores a physiological need for stability and high catalytic activity that likely predated proteins in the RNA world. In addition to divalent metals such as Ca, Mg, and Zn, monovalent cations often function as efficient and selective promoters of catalysis. Advances in structural biology unravel a rich repertoire of molecular mechanisms for enzyme activation by Na and K Strategies range from short-range effects mediated by direct participation in substrate binding, to more distributed effects that propagate long-range to catalytic residues. This review addresses general considerations and examples.
Topics: Catalysis; Cations, Monovalent; Enzymes; Potassium; Sodium
PubMed: 27462078
DOI: 10.1074/jbc.R116.737833 -
Journal of the American Society of... Jun 2023Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular...
SIGNIFICANCE STATEMENT
Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular K + concentration in kidney tissue is increasingly recognized as an important regulator of K + secretion, the underlying mechanisms that are relevant in vivo remain controversial. To assess the role of the signaling kinase mTOR complex-2 (mTORC2), the authors compared the effects of K + administered by gavage in wild-type mice and knockout mice with kidney tubule-specific inactivation of mTORC2. They found that mTORC2 is rapidly activated to trigger K + secretion and maintain electrolyte homeostasis. Downstream targets of mTORC2 implicated in epithelial sodium channel regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. These findings offer insight into electrolyte physiologic and regulatory mechanisms.
BACKGROUND
Increasing evidence implicates the signaling kinase mTOR complex-2 (mTORC2) in rapid renal responses to changes in plasma potassium concentration [K + ]. However, the underlying cellular and molecular mechanisms that are relevant in vivo for these responses remain controversial.
METHODS
We used Cre-Lox-mediated knockout of rapamycin-insensitive companion of TOR (Rictor) to inactivate mTORC2 in kidney tubule cells of mice. In a series of time-course experiments in wild-type and knockout mice, we assessed urinary and blood parameters and renal expression and activity of signaling molecules and transport proteins after a K + load by gavage.
RESULTS
A K + load rapidly stimulated epithelial sodium channel (ENaC) processing, plasma membrane localization, and activity in wild-type, but not in knockout, mice. Downstream targets of mTORC2 implicated in ENaC regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. We observed differences in urine electrolytes within 60 minutes, and plasma [K + ] was greater in knockout mice within 3 hours of gavage. Renal outer medullary potassium (ROMK) channels were not acutely stimulated in wild-type or knockout mice, nor were phosphorylation of other mTORC2 substrates (PKC and Akt).
CONCLUSIONS
The mTORC2-SGK1-Nedd4-2-ENaC signaling axis is a key mediator of rapid tubule cell responses to increased plasma [K + ] in vivo . The effects of K + on this signaling module are specific, in that other downstream mTORC2 targets, such as PKC and Akt, are not acutely affected, and ROMK and Large-conductance K + (BK) channels are not activated. These findings provide new insight into the signaling network and ion transport systems that underlie renal responses to K +in vivo .
Topics: Mice; Animals; Phosphorylation; Potassium; Epithelial Sodium Channels; Protein Serine-Threonine Kinases; Potassium, Dietary; TOR Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Immediate-Early Proteins; Mechanistic Target of Rapamycin Complex 2; Kidney; Carrier Proteins; Mice, Knockout; Ion Transport
PubMed: 36890646
DOI: 10.1681/ASN.0000000000000109 -
Nutrition & Dietetics: the Journal of... Feb 2020The potential renal acid load (PRAL) has been described in relation to different health outcomes. Outcomes over time and conclusions made are often based on baseline...
AIM
The potential renal acid load (PRAL) has been described in relation to different health outcomes. Outcomes over time and conclusions made are often based on baseline dietary intake values. However, to study reliable long-term associations, parameters calculated based on dietary intake data, such as PRAL, must be stable over time. Therefore, the aim of the present study was to assess the stability of PRAL and its components over a 10-year time period.
METHODS
PRAL values of three-day dietary intake data from 197 women and 373 men on two assessment moments (2002-2004 and 2012-2014) were calculated. Pearson correlation and intra-class correlation coefficients were used for assessing the stability of PRAL and its components. Level of agreement between the two assessment moments was estimated after splitting up subjects in quintiles of PRAL, calculating kappa values and changes of quintiles over time.
RESULTS
No significant differences in mean PRAL over time were found. Stability of PRAL and its components was low. Poor agreement between the first and second assessment was shown by low kappa values and change of most of the subjects to an adjacent and non-adjacent quintile after 10 years.
CONCLUSIONS
Based on nutrition assessments carried out using three-day dietary records, stability of PRAL over a 10-year time period could not be confirmed, even though no significant difference between mean PRAL and its components over time was found. Therefore, interpretation of longitudinal outcomes based on PRAL and its component calculated at baseline should be interpreted with caution.
Topics: Adolescent; Adult; Aged; Body Mass Index; Calcium, Dietary; Databases, Factual; Diet; Diet Records; Dietary Proteins; Female; Follow-Up Studies; Humans; Hydrogen-Ion Concentration; Kidney; Longitudinal Studies; Male; Middle Aged; Nutrition Assessment; Phosphorus, Dietary; Potassium, Dietary; Young Adult
PubMed: 29732678
DOI: 10.1111/1747-0080.12432 -
The Journal of General Physiology Oct 2021The ability to discriminate between different ionic species, termed ion selectivity, is a key feature of ion channels and forms the basis for their physiological...
The ability to discriminate between different ionic species, termed ion selectivity, is a key feature of ion channels and forms the basis for their physiological function. Members of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily of trimeric ion channels are typically sodium selective, but to a surprisingly variable degree. While acid-sensing ion channels (ASICs) are weakly sodium selective (sodium:potassium ratio ∼10:1), ENaCs show a remarkably high preference for sodium over potassium (>500:1). This discrepancy may be expected to originate from differences in the pore-lining second transmembrane segment (M2). However, these show a relatively high degree of sequence conservation between ASICs and ENaCs, and previous functional and structural studies could not unequivocally establish that differences in M2 alone can account for the disparate degrees of ion selectivity. By contrast, surprisingly little is known about the contributions of the first transmembrane segment (M1) and the preceding pre-M1 region. In this study, we used conventional and noncanonical amino acid-based mutagenesis in combination with a variety of electrophysiological approaches to show that the pre-M1 and M1 regions of mASIC1a channels are major determinants of ion selectivity. Mutational investigations of the corresponding regions in hENaC show that these regions contribute less to ion selectivity, despite affecting ion conductance. In conclusion, our work suggests that the remarkably different degrees of sodium selectivity in ASICs and ENaCs are achieved through different mechanisms. These results further highlight how M1 and pre-M1 are likely to differentially affect pore structure in these related channels.
Topics: Acid Sensing Ion Channels; Epithelial Sodium Channels; Ions; Potassium; Sodium
PubMed: 34436511
DOI: 10.1085/jgp.202112899 -
Small (Weinheim An Der Bergstrasse,... Jan 2022Soft carbon (SC) has become a promising anode for potassium ion batteries (PIBs) benefiting from its structural flexibility. However, the evolution of potassium storage...
Soft carbon (SC) has become a promising anode for potassium ion batteries (PIBs) benefiting from its structural flexibility. However, the evolution of potassium storage behavior with the microstructure (the average size of the crystallites L and the average interlayer spacing a ) is still unclear, which hinders the understanding of the potassium storage mechanism. Herein, a series of soft carbon with different microstructures is prepared through pyrolysis of petroleum pitch. Based on the analysis of the relationship between electrochemical behavior and microstructure, an adsorption-insertion mechanism is proposed: the capacity in the voltage range of 0.45-1.1 V is originated from the adsorption of potassium ions on edge-defect sites whereas the capacity below 0.45 V is attributed to the insertion of potassium ions into interlayers. When L equals to 10.56 Å, SCs exhibit an adsorption-controlled mechanism. However, as L increases to 120.98 Å, the insertion process is dominant. With L increasing from 21.9 to 93.02 Å, SCs have two mixed behaviors. The initial insertion coefficients do not change until a decreases to 3.46 Å. These findings highlight the relation of potassium storage behavior with different microstructures and the adsorption-insertion mechanism can provide insights into the design of SC anodes for PIBs.
Topics: Adsorption; Carbon; Electric Power Supplies; Ions; Potassium
PubMed: 34841653
DOI: 10.1002/smll.202105275 -
Advanced Materials (Deerfield Beach,... Oct 2023Living cells efflux intracellular ions for maintaining cellular life, so intravital measurements of specific ion signals are of significant importance for studying...
Living cells efflux intracellular ions for maintaining cellular life, so intravital measurements of specific ion signals are of significant importance for studying cellular functions and pharmacokinetics. In this work, de novo synthesis of artificial K -selective membrane and its integration with polyelectrolyte hydrogel-based open-junction ionic diode (OJID) is demonstrated, achieving a real-time K -selective ion-to-ion current amplification in complex bioenvironments. By mimicking biological K channels and nerve impulse transmitters, in-line K -binding G-quartets are introduced across freestanding lipid bilayers by G-specific hexylation of monolithic G-quadruplex, and the pre-filtered K flow is directly converted to amplified ionic currents by the OJID with a fast response time at 100 ms intervals. By the synergistic combination of charge repulsion, sieving, and ion recognition, the synthetic membrane allows K transport exclusively without water leakage; it is 250× and 17× more permeable toward K than monovalent anion, Cl , and polyatomic cation, N-methyl-d-glucamine , respectively. The molecular recognition-mediated ion channeling provides a 500% larger signal for K as compared to Li (0.6× smaller than K ) despite the same valence. Using the miniaturized device, non-invasive, direct, and real-time K efflux monitoring from living cell spheroids is achieved with minimal crosstalk, specifically in identifying osmotic shock-induced necrosis and drug-antidote dynamics.
Topics: Ion Channels; G-Quadruplexes; Biological Transport; Cations; Cell Physiological Phenomena; Potassium
PubMed: 37433455
DOI: 10.1002/adma.202303655 -
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