Extracellular Cations Research Articles

Structure-Activity Relationship of Inositol Thiophosphate Analogs as Allosteric Activators of Clostridioides difficile Toxin B.

Clostridioides difficile is a bacterium that causes life-threatening intestinal infections. Infection symptoms are mediated by a toxin secreted by the bacterium. Toxin pathogenesis is modulated by the intracellular molecule, inositol-hexakisphosphate (IP6). IP6 binds to a cysteine protease domain (CPD) on the toxin, inducing autoproteolysis, which liberates a virulence factor in the cell cytosol. We developed second-generation IP6 analogs designed to induce autoproteolysis in the gut lumen, prior to toxin uptake, circumventing pathogenesis. We synthesized a panel of thiophosphate-/sulfate-containing IP6 analogs and characterized their toxin binding affinity, autoproteolysis induction, and cation interactions. Our top candidate was soluble in extracellular cation concentrations, unlike IP6. The IP6 analogs were more negatively charged than IP6, which improved affinity and stabilization of the CPD, enhancing toxin autoproteolysis. Our data illustrate the optimization of IP6 with thiophosphate biomimetic which are more capable of inducing toxin autoproteolysis than the native ligand, warranting further studies in vivo.

Glial cells of the central and peripheral nervous systems: An overview of existing research

Orientation: Until recently, most of that neural research was been directed at understanding the morphology and functions of the neuron. However, with advances in scanning and microscopy, the morphology and function of glia are attracting greater attention.Research purpose: To many readers glia are often mysterious background players. This paper is an overview of existing literature was compiled to remove some of this mystery they may encounter when reading modern scientific neuroscience publications.Motivation for the study: This study was motivated to increase understanding of the important roles played by glia cells in the efficient operation of the human nervous system.Research approach or design and method: This study was compiled in the form of a literature review from freely accessible journal articles and common text books. Using key words ProQuest and Google Scholar databases were consulted for peer reviewed journal articles.Main findings: Glia cells have a greater role than just ‘glue’ for neurons. Examples of their roles include maintaining the levels of essential extracellular cations such as calcium, the maintaining of the integrity of neural connectivity, the creation and release of communicating gliotransmitters, and the role of microglia as an integral part of the immune system.Implications for practice: It is essential for anyone wanting to comprehend the mammalian nervous system as described in modern literature to have a broad understanding of the integration, signalling, and structural significance of glia. This overview provides a level of knowledge meeting this need.Contribution or value-add: This overview has provided a basic, but comprehensive, low-cost launch-pad of knowledge to have a broad understanding of the integration, signalling, and structural significance of glia.

Edelman Gamblegrams: a tool to teach and learn disorders of water/plasma tonicity homeostasis.

This article introduces an innovative teaching and learning tool called "Edelman Gamblegrams" that aims to help medical learners better understand disorders related to water/plasma tonicity homeostasis, i.e., hyponatremia and hypernatremia. Gamblegrams, named after physician James L. Gamble, are bar diagrams displaying the relative abundance of extracellular anions and cations and are commonly used in the analysis of acid-base disorders. The Edelman equation represents the physiological variables that determine plasma sodium concentration, namely, total body sodium mass, total body potassium mass, and total body water volume. Edelman Gamblegrams inspired by traditional Gamblegrams but using the components of the Edelman equation, visually demonstrate how sodium, potassium, and water contribute to plasma sodium concentration under normal and pathological conditions. Scenarios that lead to hypotonic hyponatremia and hypernatremia in Edelman Gamblegrams are also discussed. Furthermore, examples of how these visual aids can enhance understanding of the pathogenesis of dysnatremias are also presented. Overall, the use of Edelman Gamblegrams has the potential to improve comprehension and retention of concepts related to water/plasma tonicity homeostasis.NEW & NOTEWORTHY This article introduces a new teaching tool called "Edelman Gamblegrams," modeled after the conventional Gamblegrams used in acid-base disorder analysis and using the independent physiological variables that determine the plasma sodium concentration (Edelman equation), that aims to help medical learners understand disorders related to water/plasma tonicity homeostasis.

Verification of analytical performance of sodium assay on the Abbott architect ci8200: Experience of the central laboratory Mohammed VI Oujda

Introduction: Sodium is the main extracellular cation. It plays a fundamental role in maintaining osmotic pressure and hydroelectrolyte balance, and is therefore implicated in many pathological conditions. Sodium determination is a basic biochemistry laboratory test. Objective: the aim of our work is to verify the method of sodium determination by potentiometry on the Architect CI 8200 automated system (Abbott), in order to meet the quality requirements for laboratory accreditation under standard NF ISO 15189. Materials and methods: following the recommendations of NF EN ISO 15189, we evaluated the repeatability, intermediate precision, accuracy and uncertainty of measurement of the serum sodium assay on the Architect CI 8100 automated system, as well as a mirror comparison of the two Architect CI 8100 1 and 2. The CV values obtained were compared with those set by learned societies (SFBC and RICOS). Results and discussion: The results obtained show satisfactory repeatability for the 3 low, medium and high levels, with CV1= 1.1%, CV2=0.8% and CV3= 0.76% respectively, and satisfactory intra-laboratory reproducibility for the 3 low, medium and high levels, with CV1= 1.05%, CV2= 0.95% and CV3= 0.75% respectively. For comparison, the Bland-Altman diagram showed that the mean bias between the two automata was of the order of 0.29%, the correlation coefficient r= 0.98 with a mean difference of 0.40 mmol/l, a standard deviation of 0.675 mmol/l and a linear regression equation Y = 1.027 X - 4.073. Corrective measures were envisaged to remedy the various errors identified. To solve any malfunction in a sustainable way, it is essential to search for the anomaly by applying the Ishikawa diagram. Conclusion: The results obtained have enabled us to verify the performance of the sodium assay method and compare it with the analytical objectives set, in order to meet the regulatory and normative requirements to which our laboratory is committed.

Magnesium at physiological pregnancy and at its complications

Sources of literature on the role of the trace element magnesium and the assosiation with calcium in physiological processes in the body of reproductive aged women and pregnant women, the importance of its main functions and role in preventing the main pregnancy complications were analyzed.
 Magnesium is the fourth most important extracellular cation after sodium, potassium and calcium and the second intracellular cation in importance after potassium. Many researchers have proven the participation of magnesium in almost everyone important functions in the body. Magnesium performs the following functions which are closely interconnected: metabolic, energetic, enzymatic, cardiovascular, antithrombotic, vascular, neuroprotective, structural, is an antagonist of calcium and an agonist of NMDA receptors. Magnesium realizes its functions in close interaction with cations of sodium, potassium and calcium. It acts as a calcium antagonist. It should be noted attention to the understanding of the interaction of divalent cations-competitors of magnesium and calcium. Calcium has complex influences on interaction of magnesium with blood proteins, reduces its concentration, which can affect physiological processes during pregnancy and in non-pregnant women.
 Today, magnesium is used only for prevention and treatment of eclampsia, in which anticonvulsants are commonly used ineffective. It can be assumed that different convulsive states have different intracellularly or extracellularly magnesium concentration is important in the pathogenesis and occurrence of eclampsia. Determination of magnesium concentration never was indicated in the recommendations for the management of preeclampsia. Magnesium use is insufficiently substantiated in cases of uterus contraction activity in any conditions (threat of abortion, premature birth) and prevention of pathological blood clot formation (as causes of multiple complications of pregnancy), neuroprotective effect on a child.
 The role of magnesium in the production of steroid hormones has been proven. However, this effect remains unrealized in obstetrics and gynecology practice.
 Data from literature sources given in the article help justify the use of magnesium and analyze its interaction with calcium during pregnancy.

Enhancement of cyanobacterial blooms buoyancy by controlling extracellular polysaccharides content and cation concentration under light-limited condition

Enhancement of cyanobacterial blooms buoyancy by controlling extracellular polysaccharides content and cation concentration under light-limited condition

Characterization of a cadmium-resistant functional bacteria (Burkholderia sp. SRB-1) and mechanism analysis at physiochemical and genetic level.

In this study, the capacity of cadmium (Cd)-resistant plant growth-promoting bacteria (PGPB) Burkholderia sp. SRB-1 (SRB-1) and its mechanisms were explored through morphological characterizations, biochemical response, plant growth-promoting traits, and functional gene expression patterns. The results showed that SRB-1 was an excellent Cd-resistant bacteria (MIC was 420mg L-1), and its maximum Cd removal rate reached 72.25%. Biosorption was the main removal method of Cd for SRB-1, preventing intracellular Cd accumulation and maintaining cellular metabolism. Various functional groups on the cell wall were involved in Cd binding, which deposited as CdS and CdCO3 on the cell surface according to XPS analysis and might be critical for reducing Cd physiochemical toxicity. Furthermore, metals exporting (zntA, czcA, czcB, czcC), detoxification (dsbA, cysM), and antioxidation (katE, katG, SOD1) related genes were annotated in the SRB-1 genome. The results of Cd distribution and antioxidative enzyme activity in SRB-1 also illustrated that Cd2+ efflux and antioxidative response were the main intracellular Cd-resistant mechanisms. These conclusions were further verified by qRT-PCR analysis. Overall, the strategies of extracellular biosorption, cation efflux, and intracellular detoxification jointly build the Cd-resistant system, which invested Burkholderia sp. SRB-1 with potential for bioremediation in heavily Cd-contaminated environmental sites.

Impact on AChR open channel noise by pore-peripheral salt bridge depends on voltage and divalent cations

Mechanisms behind the fluctuations in the ionic current through single acetylcholine receptor (AChR) channels have remained elusive. In a recent study of muscle AChR we showed that mutation of a conserved intramembrane salt bridge in the β- and δ-subunits markedly increased fluctuations in the open channel current that extended from low to high frequency. Here, we show that extracellular divalent cations reduce the high-frequency fluctuations and increase the low-frequency fluctuations. The low-frequency fluctuations are shown to arise from steps between two current levels, with the ratio of the time at each level changing e-fold for a 70 mV increase in membrane potential, indicating modulation by a charged element within the membrane field. Increasing the charge on the ion selectivity filter biases the ratio of current levels equivalent to a 50 mV increase in membrane potential but does not alter the voltage dependence of the ratio. The magnitudes of the voltage dependence and voltage bias allow estimates of the distance between the ion selectivity filter and the voltage-sensing element. Studies with either calcium or magnesium show that the two divalent cations synergize to increase the low-frequency fluctuations, whereas they act independently to decrease the high-frequency fluctuations, indicating multiple divalent cation binding sites. Molecular dynamics simulations applied to the structure of the Torpedo AChR reveal that mutation of the salt bridge alters the equilibrium positions and dynamics of residues local to the site of the mutation and within the adjacent ion selectivity filter in a calcium-dependent manner. Thus, disruption of a conserved intramembrane salt bridge in the muscle AChR induces fluctuations in open channel current that are sensitive to divalent cation binding at multiple sites and modulated by a charged element within the membrane field.

Extracellular Cysteines Are Critical to Form Functional Cx46 Hemichannels.

Connexin (Cxs) hemichannels participate in several physiological and pathological processes, but the molecular mechanisms that control their gating remain elusive. We aimed at determining the role of extracellular cysteines (Cys) in the gating and function of Cx46 hemichannels. We studied Cx46 and mutated all of its extracellular Cys to alanine (Ala) (one at a time) and studied the effects of the Cys mutations on Cx46 expression, localization, and hemichannel activity. Wild-type Cx46 and Cys mutants were expressed at comparable levels, with similar cellular localization. However, functional experiments showed that hemichannels formed by the Cys mutants did not open either in response to membrane depolarization or removal of extracellular divalent cations. Molecular-dynamics simulations showed that Cys mutants may show a possible alteration in the electrostatic potential of the hemichannel pore and an altered disposition of important residues that could contribute to the selectivity and voltage dependency in the hemichannels. Replacement of extracellular Cys resulted in “permanently closed hemichannels”, which is congruent with the inhibition of the Cx46 hemichannel by lipid peroxides, through the oxidation of extracellular Cys. These results point to the modification of extracellular Cys as potential targets for the treatment of Cx46-hemichannel associated pathologies, such as cataracts and cancer, and may shed light into the gating mechanisms of other Cx hemichannels.

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion. The initial approach is similar in most cases, but a definitive treatment depends on etiology, that is why etiological investigation is mandatory in all cases. The majority of patients are asymptomatic and diagnosed during routine exams; only a small percentage of patients present with severe manifestations which can affect neurological, muscular, gastrointestinal, renal, and cardiovascular systems. Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms. Critically ill patients should receive treatment as soon as diagnosis is made. Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption such as bisphosphonates and, more recently, denosumab, in refractory cases; also, corticosteroids and calcitonin can be used in specific cases. This review aims to provide a clinical update on current concepts of the pathophysiology of calcium homeostasis, epidemiology, screening, clinical presentation, diagnosis, and management of hypercalcemia.

Cross Sectional Study on Hyponatremia

Introduction: Sodium is the major extracellular cation, playing important role in maintaining homeostasis. Normal level of serum sodium is between 136-145 mmol/L. Hyponatremia (<136mmol/L) can present with nausea, vomiting, confusion, lethargy, disorientation.Severe hyponatremia (<125mmol/L) can present with seizures, coma or death.
 Methods: Our study was a cross sectional, retrospective study including 100 subjects of hyponatremia.
 Results: In our study, we analyzed the age-wise distribution, severity and various causes of hyponatremia in each grade of hyponatremia based on severity.
 Conclusion: Drug-induced hyponatremia is a more prevalent and a preventable cause and can be avoided by proper monitoring of patients.

Effects of divalent cations on Schaffer collateral axon function.

Previously, we reported that distal Schaffer collaterals undergo biphasic changes in excitability during high-frequency stimulation (HFS), with an early hyper-excitability period followed by an excitability depression period. The extracellular divalent cations calcium and magnesium can regulate membrane excitability in neuronal tissue. Therefore, we hypothesized that altering the concentrations of extracellular calcium and magnesium would alter the biphasic excitability changes. We tested this hypothesis by recording distal Schaffer collateral fiber volleys in stratum radiatum of hippocampal area CA1 during 100Hz HFS in artificial cerebral spinal fluid (ACSF) containing normal and altered concentrations of extracellular divalent cations. Our normal ACSF contained 2.0mM calcium and 2.0mM magnesium. We examined four solutions with altered divalent cation concentrations: (1) high-calcium/low-magnesium (3.8mM/0.2mM), (2) low-calcium/high-magnesium (0.2mM/3.8mM), (3) high-calcium/normal-magnesium (3.8mM/2.0mM), or (4) normal-calcium/high-magnesium (2.0mM/10.0mM), and assessed the effects on Schaffer collateral responses. Increasing or decreasing extracellular calcium enhanced or reduced (respectively) the early hyper-excitable period whereas increasing extracellular magnesium reduced the later excitability depression. Because these results might be explained by altered calcium influx through voltage-gated calcium (CaV) channels, we tested CaV blockers (ω-agatoxin IVA, ω-conotoxin-GVIA, cadmium), but observed no effects on responses during HFS. Some of the effects of altered divalent cation concentration may be explained by altered membrane surface charge. Although this mechanism does not completely explain our findings, calcium influx through CaV channels is not required.

Geometry and water accessibility of the inhibitor binding site of Na+-pump: Pulse- and CW-EPR study

Spin labels based on cinobufagin, a specific inhibitor of the Na,K-ATPase, have proved valuable tools to characterize the binding site of cardiotonic steroids (CTSs), which also constitutes the extracellular cation pathway. Because existing literature suggests variations in the physiological responses caused by binding of different CTSs, we extended the original set of spin-labeled inhibitors to the more potent bufalin derivatives. Positioning of the spin labels within the Na,K-ATPase site was defined and visualized by molecular docking. Although the original cinobufagin labels exhibited lower affinity, continuous-wave electron paramagnetic resonance spectra of spin-labeled bufalins and cinobufagins revealed a high degree of pairwise similarity, implying that these two types of CTS bind in the same way. Further analysis of the spectral lineshapes of bound spin labels was performed with emphasis on their structure (PROXYL vs. TEMPO), as well as length and rigidity of the linkers. For comparable structures, the dynamic flexibility increased in parallel with linker length, with the longest linker placing the spin label at the entrance to the binding site. Temperature-related changes in spectral lineshapes indicate that six-membered nitroxide rings undergo boat-chair transitions, showing that the binding-site cross section can accommodate the accompanying changes in methyl-group orientation. D2O-electron spin echo envelope modulation in pulse-electron paramagnetic resonance measurements revealed high water accessibilities and similar polarity profiles for all bound spin labels, implying that the vestibule leading to steroid-binding site and cation-binding sites is relatively wide and water-filled.

Structure and Function of the Human Sodium Leak Channel NALCN

The sodium leak channel (NALCN) mediates a persistent depolarising Na+ current in neurons that regulates respiration, locomotion and circadian rhythm. Despite strong clinical evidence supporting its critical role in neurodevelopment and survival, fundamental aspects of NALCN function have remained unexplored due to challenges in heterologous expression. We recently established that the robust function of NALCN in vitro requires three other neuronal proteins, namely UNC79, UNC80 and FAM155A. The resulting channel complex is constitutively active, voltage sensitive, and only conducts small monovalent cations. Moreover, extracellular divalent cations inhibit NALCN directly via a pore-blocking mechanism. These data corroborate the notion that the NALCN channel complex is directly responsible for the increased neuronal excitability in reduced extracellular Ca2+. We also determined the structure of NALCN in complex with FAM155A using cryo-electron microscopy, which revealed several unique features. For instance, FAM155A forms an extracellular dome that sterically hinders neurotoxin access to the selectivity filter. Together with occluded lateral fenestrations that typically serve as entryways for lipophilic drugs, these features provide a simple explanation for the lack of NALCN pharmacology. Structural mapping of disease mutations highlighted the intracellular activation gate as a hotspot for gain-of-function mutations. Our findings suggest these residues participate in intra- and interdomain interactions, and even subtle, conservative substitutions may disrupt these networks to elevate channel activity. Together, we have performed the first in-depth biophysical characterisation of the NALCN channel complex, and provided unprecedented glimpses into the architecture of this physiologically important protein.

Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration

The design of orthopedic biomaterials has gradually shifted from “immune-friendly” to “immunomodulatory,” in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration. Despite the well-known effects of bioactive metallic ions on osteogenesis, how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied. Herein, we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation (Mg2+) in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid (PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions. The results suggest that the Mg2+-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory (IL-10) and pro-osteogenic (BMP-2 and TGF-β1) cytokines production. It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. The in vivo results further verify that a large amount of bony tissue, with comparable bone mineral density and mechanical properties, has been generated at an early post-surgical stage in rat intramedullary bone defect models. This study demonstrates that the concept of in situ immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.

Low serum sodium concentrations in patients with obesity normalizes with weight loss.

Obesity is associated with higher extracellular fluid (ECF) compared to intracellular fluid (ICF) volume and this dysregulation is associated with hypertension and abdominal obesity, associated with metabolic syndrome. As sodium is predominantly an extracellular cation, a higher ECF/ICF ratio will lower serum sodium concentration. The aim of the study was to see whether weight loss, due to dieting and bariatric surgery, had any impact on serum sodium concentrations in patients with severe obesity. Patients with a BMI ≥35kg/m2 admitted for bariatric surgery at Innlandet Hospital Trust, Norway during 2012-14 were included in the study (n=119). Clinical data and blood samples were recorded at inclusion, after mean six months of dieting, as well as six and 12 months after bariatric surgery. At inclusion, mean serum sodium was in the lower normal range, 138.3 (SD 2.4) mmol/L, but increased to 141.8 (SD 1.9) mmol/L after weight loss. The increase was significantly correlated to total weight loss (rho: 0.29, p=0.007). Twelve months after surgery, serum sodium was significantly higher in patients with a normal BMI (<25kg/m2) compared to patients with overweight. Obesity and hypertension are associated with body fluid dysregulation affecting serum sodium concentrations. As mild hyponatremia, even within the normal sodium range, is associated with increased total mortality and major cardiovascular disease events, serum sodium might be a potential risk marker in patients with obesity.

Effects of Lactate on One Class of Group III (CT3) Muscle Afferents

A class of Group III muscle afferent neurons has branching sensory terminals in the connective tissue between layers of mouse abdominal muscles (“CT3 muscle afferents”). These sensory endings are both mechanosensitive and metabosensitive. In the present study, responses of CT3 afferents to lactate ions and changes in temperature were recorded. Raising muscle temperature from 32.7°C to 37°C had no consistent effects on CT3 afferent basal firing rate or responses to either von Frey hair stimulation or to an applied load. Superfusion with lactate ions (15 mM, pH 7.4) was associated with an increase in firing from 6 ± 0.7 Hz to 11.7 ± 6.7 Hz (14 units, n = 13, P < 0.05, P = 0.0484) but with considerable variability in the nature and latency of response. Reducing the concentration of extracellular divalent cations, which mimicked the chelating effects of lactate, did not increase firing. Raised concentrations of divalent cations (to compensate for chelation) did not block excitatory effects of lactate on CT3 afferents, suggesting that effects via ASIC3 were not involved. Messenger RNA for the G-protein coupled receptor, hydroxyl carboxylic acid receptor 1 (HCAR1) was detected in dorsal root ganglia and HCAR1-like immunoreactivity was present in spinal afferent nerve cell bodies retrogradely labeled from mouse abdominal muscles. HCAR1-like immunoreactivity was also present in axons in mouse abdominal muscles. This raises the possibility that some effects of lactate on group III muscle afferents may be mediated by HCAR1.

Voltage-gated ion channels mediate the electrotaxis of glioblastoma cells in a hybrid PMMA/PDMS microdevice.

Transformed astrocytes in the most aggressive form cause glioblastoma, the most common cancer in the central nervous system with high mortality. The physiological electric field by neuronal local field potentials and tissue polarity may guide the infiltration of glioblastoma cells through the electrotaxis process. However, microenvironments with multiplex gradients are difficult to create. In this work, we have developed a hybrid microfluidic platform to study glioblastoma electrotaxis in controlled microenvironments with high throughput quantitative analysis by machine learning-powered single cell tracking software. By equalizing the hydrostatic pressure difference between inlets and outlets of the microchannel, uniform single cells can be seeded reliably inside the microdevice. The electrotaxis of two glioblastoma models, T98G and U-251MG, requires an optimal laminin-containing extracellular matrix and exhibits opposite directional and electro-alignment tendencies. Calcium signaling is a key contributor in glioblastoma pathophysiology but its role in glioblastoma electrotaxis is still an open question. Anodal T98G electrotaxis and cathodal U-251MG electrotaxis require the presence of extracellular calcium cations. U-251MG electrotaxis is dependent on the P/Q-type voltage-gated calcium channel (VGCC) and T98G is dependent on the R-type VGCC. U-251MG electrotaxis and T98G electrotaxis are also mediated by A-type (rapidly inactivating) voltage-gated potassium channels and acid-sensing sodium channels. The involvement of multiple ion channels suggests that the glioblastoma electrotaxis is complex and patient-specific ion channel expression can be critical to develop personalized therapeutics to fight against cancer metastasis. The hybrid microfluidic design and machine learning-powered single cell analysis provide a simple and flexible platform for quantitative investigation of complicated biological systems.

Pathophysiology of Drug-Induced Hypomagnesaemia.

Magnesium (Mg2+) is the second most abundant intracellular and fourth extracellular cation found in the body and is involved in a wide range of functions in the human cell and human physiology. Its role in most of the enzyme processes (ATP-ases)-stabilisation of nucleic acids (DNA, RNA), regulation of calcium and potassium ion channels, proliferation, glucose metabolism and apoptosis-make it one of the most important cations in the cell. Three pathogenetic mechanisms are mainly implicated in the development of hypomagnesaemia: reduced food intake, decreased intestinal absorption and increased renal excretion of Mg2+. This review presents the function of Mg2+, how it is handled in the kidney and the drugs that cause hypomagnesaemia. The frequency and the number of drugs like diuretics and proton-pump inhibitors (PPIs) that are used daily in medical practice are discussed in order to prevent and treat adverse effects by providing an insight into Mg2+ homeostasis.

Does ENaC Work as Sodium Taste Receptor in Humans?

Taste reception is fundamental for the proper selection of food and beverages. Among the several chemicals recognized by the human taste system, sodium ions (Na+) are of particular relevance. Na+ represents the main extracellular cation and is a key factor in many physiological processes. Na+ elicits a specific sensation, called salty taste, and low-medium concentrations of table salt (NaCl, the common sodium-containing chemical we use to season foods) are perceived as pleasant and appetitive. How we detect this cation in foodstuffs is scarcely understood. In animal models, such as the mouse and the rat, the epithelial sodium channel (ENaC) has been proposed as a key protein for recognizing Na+ and for mediating preference responses to low-medium salt concentrations. Here, I will review our current understanding regarding the possible involvement of ENaC in the detection of food Na+ by the human taste system.