Intracellular Cation Research Articles

Mg2+ binding to Coenzyme A

Magnesium (Mg2+), the second most abundant intracellular cation, plays a crucial role in cellular functions. In this study, we investigate the interaction between Mg2+ and coenzyme A (CoA), a thiol-containing cofactor central to cellular metabolism also involved in protein modifications. Isothermal titration calorimetry revealed a 1:1 binding stoichiometry between Mg2+ and free CoA under biologically relevant conditions. Association constants of (537 ± 20) M-1 and (312 ± 7) M-1 were determined at 25°C and pH 7.2 and 7.8, respectively, suggesting that a significant fraction of CoA is likely bound to Mg2+ both in the cytosol and in the mitochondrial matrix. Additionally, the process is entropically-driven, and our results support that the origin of the entropy gain is solvent-related. On the other hand, the combination of 1- and 2-dimensional nuclear magnetic resonance spectroscopy with molecular dynamics simulations and unsupervised learning demonstrate a direct coordination between Mg2+ and the phosphate groups of the 4-phosphopantothenate unit and bound to position 5’ of the adenosine ring. Interestingly, the phosphate in position 3' only indirectly contributes to Mg2+ coordination. Finally, we discuss how the binding of Mg2+ to CoA perturbates the chemical environment of different CoA atoms, regardless of their apparent proximity to the coordination site, through the modulation of the CoA conformational landscape. This insight holds implications for understanding the impact on both CoA and Mg2+ functions in physiological and pathological processes.

7193 Hypocalcemia: Pitfalls, Paradoxes, And Conundrums

Abstract Disclosure: K. Dash: None. P. Eswaran: None. K. Maharajan: None. S. Nangia: None. U. Ayyagari: None. 58 year old female with PV bleed was diagnosed as Carcinoma Cervix and recommended radical radiotherapy with 6 weeks of concurrent chemotherapy with Cisplatin and IV Magnesium premedication. Post 6th cycle of chemo, she presented with nausea, perioral and facial tingling, and lower limb cramps of one day duration. Investigations showed Serum Magnesium 0.4 mg/dl (range 1.6–2.5), Calcium 5.9 mg/dl (8.4-10.2), Potassium 3.3 mg/dl (3.5-5.5). She was treated with IV Calcium gluconate and discharged home post correction with serum Calcium 7.9, Magnesium 1.8, PTH 88.7. She was readmitted twice, 5 and 9 days later, with hypocalcemia, given IV Calcium Gluconate, and discharged post correction of serum calcium levels. She presented to Endocrine OP 2 days later, asymptomatic, serum Calcium 5.9, Magnesium 0.6, K 3.8. She was admitted and replacement commenced with IV Magnesium and Calcium. Over the next day her Calcium and Magnesium levels improved. She was stabilized on oral Calcium and Magnesium replacement and discharged. Calcium replacement was weaned over the next 2 weeks with stable serum Calcium levels on continuing oral Magnesium replacement to date. Cisplatin is a commonly used chemotherapeutic agent. It binds to the N7 reactive center on purine residues and causes DNA damage in cancer cells blocking cell division resulting in apoptotic cell death. This interaction with DNA and the formation of covalent adducts with purine DNA bases is the source of the cytotoxic effect of cisplatin. Therapy is associated with side effects including neuro-, nephro-, hepato-, and cardiotoxicity. Electrolyte disturbances including hypomagnesemia, hypocalcemia, hypokalemia, and hyponatremia are recognized in association with cisplatin therapy. The signs and symptoms of dyselectrolytemias may be nonspecific and a high index of suspicion is required to diagnose. Hypomagnesemia is described in up to 78% of patients on cisplatin due to magnesium wasting attributed to reduced magnesium reabsorption in the distal tubule and/or inadequate intestinal magnesium absorption. Magnesium is primarily an intracellular cation and stored in bone. Serum levels are a poor indicator of total body magnesium and serum concentrations <1.8 mg/dl indicate more severe underlying deficit. Hypocalcemia, possibly due to end organ unresponsiveness to PTH, frequently coexists with hypomagnesimia, and can be resistant to treatment unless hypomagnesimia is corrected. While hypomagnesimia stimulates PTH secretion, very low serum concentrations can induce a paradoxical block. Our case illustrates the importance of recognizing and correcting underlying hypomagnesimia to stabilize serum calcium levels. The normal PTH level, despite low serum Calcium, suggests hypomagnesimia impairing parathyroid gland function. Due to the acute presentation, and ongoing IV correction, we were unable to measure urinary magnesium excretion. Presentation: 6/1/2024

Accumulation of Li+ Ions Triggers Changes in FOS, JUN, EGR1, and MYC Transcription in the LiCl-Treated Human Umbilical Vein Endothelial Cells (HUVEC).

Changes in intracellular concentrations of Na+ and K+ are shown to alter gene expression. Another monovalent cation, Li+, is well known as a medicine for treatment of psychiatric disorders, but mechanism of its action is obscure. Thus, it is important to evaluate the effect of Li+ on gene expression in endothelial cells. Here we studied influence of the increased intracellular Na+ or Li+ concentrations on transcription of Na+i/K+i-sensitive genes. Treatment of the human endothelial cells (HUVEC) with LiCl for 1.5h resulted in accumulation of Li+ in the cells. This was followed by increase in the FOS and EGR1 mRNAs levels and decrease in the JUN and MYC mRNA levels. Treatment of HUVEC with the Na+-ionophore monensin led to accumulation of Na+ and loss of K+ ions. However, monensin had no significant effect on gene expression. Incubation of HUVEC with elevated extracellular NaCl concentration increased intracellular K+ concentration and transcription of the ATF3 gene, while transcription of the JUN gene decreased. These results indicate that Na+ and Li+ ions have different effects on the gene expression profile in the cells that is likely associated with the fact that they affect differently the intracellular monovalent cations ratio.

Magnesium Sulfate, Rosuvastatin, Sildenafil and Their Combination in Chronic Hypoxia-Induced Pulmonary Hypertension in Male Rats.

Previous experimental findings have led to considerable interest in the beneficial effects on pulmonary hypertension (PH) produced by sildenafil and in the pleiotropic effects of rosuvastatin and their positive role in the process of pulmonary angiogenesis. However, magnesium sulfate, the most abundant intracellular cation, is essential in vascular endothelial functionality due to its anti-inflammatory and vasodilatory effects. Therefore, the present study aims to assess these treatment regimens and how they could potentially provide some additional benefits in PH therapy. Fourteen days after chronic-hypoxia PH was induced, rosuvastatin, sildenafil and magnesium sulfate were administered for an additional fourteen days to male Wistar rats. The Fulton Index, right ventricle (RV) anterior wall thickness, RV internal diameter and pulmonary arterial (PA) acceleration time/ejection time were evaluated, and another four biochemical parameters were calculated: brain natriuretic peptide, vascular endothelial growth factor, nitric oxide metabolites and endothelin 1. The present study demonstrates that sildenafil and rosuvastatin have modest effects in reducing RV hypertrophy and RV systolic pressure. The drug combination of sildenafil + rosuvastatin + magnesium sulfate recorded statistically very highly significant results on all parameters; through their positive synergistic effects on vascular endothelial function, oxidative stress and pathological RV remodeling, they attenuated PH in the chronic hypoxia pulmonary hypertension (CHPH) rat model.

Abstract Tu125: Loss of mitochondrial magnesium leads to hepatic ketogenic insufficiency and accelerates the progression of cardiac hypertrophy

Magnesium (Mg 2+ ) is an abundant intracellular divalent cation and is an important co-factor. Like calcium, Mg 2+ is also compartmentalized to mitochondria. Mrs2 is the only known molecular machinery associated with mitochondrial Mg 2+ influx. Although we know that Mg 2+ plays a crucial role in cellular homeostasis, our understanding of how mMg 2+ homeostasis alters the metabolic state of the cell remains incomplete. To begin elucidating the importance of mMg 2+ , we made a liver-specific Mrs2 knockout mouse model (Mrs2 Dhep ) using the Cre-loxP system. Since liver is the central hub of lipid metabolism, we hypothesized that loss of mitochondrial Mg 2+ could alter hepatic lipid homeostasis. Enigmatically we observed increased hepatic lipid accumulation, in spite of increased PPARa activation and Fatty acid oxidation (FAO). In our previous work we showed in Mrs2 Dhep the FAO-derived acetyl CoA to be channeled to de novo lipogenesis (DNL) via cataplerosis, instead of ketogenesis. Further, our results show markedly blunted ketonemia in Mrs2 Dhep revealing a state of ketogenic insufficiency. In the presence of increased ketone bodies (KB), normal hearts preferentially use both KB and FAO while glucose metabolism tend to be reduced. During the progression of heart failure (HF), the failing heart depends on alternate ATP generating substrates like KB as there is a metabolic deficit in both FAO and glucose metabolism. Because we saw a decrease in the KB, we hypothesize that hepatic ketogenic insufficiency will lead to cardiac hypertrophy and heart failure in pressure overload model due to energy insufficiency. Interestingly we found the heart weight and the heart to body weight ratio, left ventricular (LV) wall thickness, expression of genes linked to cardiac hypertrophy to be increased in Mrs2 Dhep compared to control. We also observed an adverse structural remodeling of LV and LV dysfunction. Masson’s trichrome staining showed increased collagen deposition and fibrosis in the Mrs2 Dhep mice when compared to the control. Our results show altered hepatic mitochondrial Mg 2+ homeostasis to have profound direct effect on hepatic lipid metabolism and indirect inter-organ effect on the heart following pressure overload.

Corrélations entre la magnésémie et le diabète type 2 Correlations between magnesemia and type 2 diabetes

Magnesium plays a vital role in our bodies, as the second most important intracellular cation after potassium. It acts as a cofactor for over 300 enzymes involved in various essential physiological processes, such as carbohydrate metabolism and the regulation of insulin secretion. Any disturbance in magnesium homeostasis, notably hypomagnesemia, can lead to a variety of metabolic disorders, specifically diabetes. Indeed, the incidence of hypomagnesemia is significantly higher in diabetics than in non-diabetics, and correlates with the chronic complications of this metabolic disease. Hypomagnesemia leads to inhibition of the GLUT4 transporter, which contributes to increased insulin resistance and disrupts lipid metabolism. This literature review aims to synthesize current knowledge on variations in magnesemia in type 2 diabetes, and its association with major diabetic complications.

Maintaining mitochondrial NAD+ homeostasis is key for heat-induced skeletal muscle injury prevention despite presence of intracellular cation alterations.

Mitochondrial dysfunction is implicated in heat-induced skeletal muscle (SKM) injury and its underlying mechanisms remain unclear. Evidence suggests that cellular ions and molecules, including divalent cations and adenine nucleotides, are involved in the regulation of mitochondrial function. In this study, we examined Ca2+, Mg2+, and NAD+ levels in mouse C2C12 myoblasts and SKM in response to heat exposure. During heat exposure, mitochondrial Ca2+ levels increased significantly, whereas cytosolic Ca2+ levels remained unaltered. The mitochondrial Ca2+ levels in the SKM of heat-exposed mice were 28% higher compared to control mice. No changes in cytosolic Ca2+ were detected between the two groups. Following heat exposure, cytosolic and mitochondrial Mg2+ levels were reduced by 47% and 23% in C2C12 myoblasts, and by 51% and 44% in mouse SKMs, respectively. In addition, heat exposure decreased mitochondrial NAD+ levels by 32% and 26% in C2C12 myoblasts and mouse SKMs, respectively. Treatment with the NAD+ precursor nicotinamide riboside (NR) partially prevented heat-induced depletion of NAD+. Additionally, NR significantly reduced heat-increased mitochondrial fission, mitochondrial depolarization, and apoptosis in C2C12 myoblasts and mouse SKMs. No effects of NR on heat-induced changes in intracellular Ca2+ and Mg2+ levels were observed. This study provides in vitro and in vivo evidence that acute heat stress causes alterations in mitochondrial Ca2+, Mg2+, and NAD+ homeostasis. Our results suggest mitochondrial NAD+ homeostasis as a therapeutic target for the prevention of heat-induced SKM injury.

A non-B DNA binding peptidomimetic channel alters cellular functions

DNA binding transcription factors possess the ability to interact with lipid membranes to construct ion-permeable pathways. Herein, we present a thiazole-based DNA binding peptide mimic TBP2, which forms transmembrane ion channels, impacting cellular ion concentration and consequently stabilizing G-quadruplex DNA structures. TBP2 self-assembles into nanostructures, e.g., vesicles and nanofibers and facilitates the transportation of Na+ and K+ across lipid membranes with high conductance (~0.6 nS). Moreover, TBP2 exhibits increased fluorescence when incorporated into the membrane or in cellular nuclei. Monomeric TBP2 can enter the lipid membrane and localize to the nuclei of cancer cells. The coordinated process of time-dependent membrane or nuclear localization of TBP2, combined with elevated intracellular cation levels and direct G-quadruplex (G4) interaction, synergistically promotes formation and stability of G4 structures, triggering cancer cell death. This study introduces a platform to mimic and control intricate biological functions, leading to the discovery of innovative therapeutic approaches.

Verification of the analytical performance of the serum magnesium assay on Abbott Architect ci8200

Magnesium is recognized as the fourth most important cation in the body and the second most abundant intracellular cation, following potassium. Its physiological significance lies in its capacity to form complexes with crucial intracellular anionic ligands, notably ATP, and its ability to compete with calcium for specific binding sites on proteins and cell membranes. Over 300 enzyme reactions rely on magnesium. The concentration of free magnesium within cells determines the magnesium content of these enzymes. Magnesium influences myocardial contraction and the electrical activity of myocardial cells, as well as the specialized conduction systems of the fetus, by modulating the transmembrane movements of ions like sodium, potassium, and calcium. Furthermore, magnesium can affect the contractility of vascular smooth muscle, and alterations in intracellular magnesium levels may impact cell proliferation or contraction. Magnesium is involved in nucleic acid and protein metabolism, intermediary metabolism, energy production, and consumption reactions, and it plays specific roles in various physiological systems such as the neuromuscular and cardiovascular systems. Our research aims to assess the analytical accuracy of the serum magnesium assay method utilizing an Abbott kit on the Architect ci8200 automated system in the biochemistry laboratory of Mohammed VI University Hospital of Oujda. The evaluation of the kit's analytical accuracy was conducted within the flexible scope A by conducting a performance analysis on the Architect ci8200. We examined repeatability, reproducibility, measurement imprecision, and compared results between two Architect ci8200 instruments. All findings align with the acceptability criteria recommended by the supplier and the Valtec protocol of the Société Française de Biologie Clinique (SFBC), indicating overall satisfactory outcomes for the study. The Architect ci8200 automated system demonstrated satisfactory analytical performance for reliably determining serum magnesium levels. Method verification in medical laboratories is essential to guarantee the accuracy, precision, and reliability of test results. Verification entails confirming that the test method used is suitable for its intended purpose, yields result consistent with the claimed performance characteristics, and meets the laboratory's quality control and quality assurance standards.

Prevalence of dysmagnesemia among CKD patients in North India

Prevalence of dysmagnesemia among CKD patients in North India

Prevalence of Dysmagnesemia among Patients with Diabetes Mellitus and the Associated Health Outcomes: A Cross-Sectional Study.

Introduction: Magnesium is a vital intracellular cation crucial for over 320 enzymatic reactions related to energy metabolism, musculoskeletal function, and nucleic acid synthesis and plays a pivotal role in human physiology. This study aimed to explore the prevalence of dysmagnesemia in patients with diabetes mellitus and evaluate its correlations with glycemic control, medication use, and diabetic complications. Methods: A cross-sectional study was conducted at Sultan Qaboos University Hospital, including 316 patients aged 18 years or older with diabetes mellitus. Data included demographics, medical history, medications, and biochemical parameters. Serum total magnesium concentrations were measured, and dysmagnesemia was defined as magnesium ≤ 0.69 mmol/L for hypomagnesemia and ≥1.01 mmol/L for hypermagnesemia. Results: The prevalence of hypomagnesemia in patients with diabetes was 17.1% (95% CI: 13.3-21.7%), and hypermagnesemia was 4.1% (95% CI: 2.4-7.0%). Females were significantly overrepresented in the hypomagnesemia group, while the hypermagnesemia group showed a higher prevalence of hypertension, retinopathy, an increased albumin/creatinine ratio, chronic kidney disease (CKD), elevated creatinine levels, and a lower adjusted calcium concentration. The multinominal logistic regression exhibited that the female sex and higher serum-adjusted calcium were independent risk factors of hypomagnesemia. In contrast, the presence of hypertension, higher levels of albumin/creatinine ratio, and stage 5 CKD were independent risk factors of hypermagnesemia. Conclusions: Hypomagnesemia was common among patients with diabetes mellitus; however, hypermagnesemia was associated with microvascular complications.

House dust mite allergens induce Ca2+ signalling and alarmin responses in asthma airway epithelial cells

Type 2 inflammation in asthma develops with exposure to stimuli to include inhaled allergens from house dust mites (HDM). Features include mucus hypersecretion and the formation of pro-secretory ion transport characterised by elevated basal Cl− current. Studies using human sinonasal epithelial cells treated with HDM extract report a higher protease activated receptor-2 (PAR-2) agonist-induced calcium mobilisation that may be related to airway sensitisation by allergen-associated proteases. Herein, this study aimed to investigate the effect of HDM on Ca2+ signalling and inflammatory responses in asthmatic airway epithelial cells. Primary bronchial epithelial cells (hPBECs) from asthma donors cultured at air-liquid interface were used to assess electrophysiological, Ca2+ signalling and inflammatory responses. Differences were observed regarding Ca2+ signalling in response to PAR-2 agonist 2-Furoyl-LIGRLO-amide (2-FLI), and equivalent short-circuit current (Ieq) in response to trypsin and 2-FLI, in ALI-asthma and healthy hPBECs. HDM treatment led to increased levels of intracellular cations (Ca2+, Na+) and significantly reduced the 2-FLI-induced change of Ieq in asthma cells. Apical HDM-induced Ca2+ mobilisation was found to mainly involve the activation of PAR-2 and PAR-4-associated store-operated Ca2+ influx and TRPV1. In contrast, PAR-2, PAR-4 antagonists and TRPV1 antagonist only showed slight impact on basolateral HDM-induced Ca2+ mobilisation. HDM trypsin-like serine proteases were the main components leading to non-amiloride sensitive Ieq and also increased interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) from asthma hPBECs. These studies add further insight into the complex mechanisms associated with HDM-induced alterations in cell signalling and their relevance to pathological changes within asthma.

Hypomagnesemia-induced cerebellar syndrome: a case report

Magnesium is the second most abundant intracellular cation after potassium and is involved in over 600 enzymatic reactions that are essential for life. Hypomagnesemia (serum magnesium concentration <1.8 mg/dL (< 0.70 mmol/L)), is longstanding known to cause many clinical disorders: other electrolyte abnormalities, life-threatening arrhythmias and various neurological manifestations, from muscle cramps and myopathy, to vertigo, nystagmus, depression, acute confusional state and seizures. In the last few years some case reports have highlighted the possible existence of a peculiar hypomagnesemia induced cerebellar syndrome (HiCS). Here we present a clinical case of a 74-years-old man with severe hypomagnesemia presenting with vomiting, gait instability, diffuse tremor, associated with neuro-otological signs of cerebellar dysfunction and a MRI hyperintense lesion at cerebellar nodulus with clinico-radiological resolution after magnesium repletion.

Potassium homeostasis and therapeutic intervention with sodium zirconium cyclosilicate: A model-informed drug development case study.

Potassium (K+ ) is the main intracellular cation in the body. Elevated K+ levels (hyperkalemia) increase the risk of life-threatening arrhythmias and sudden cardiac death. However, the details of K+ homeostasis and the effects of orally administered K+ binders, such as sodium zirconium cyclosilicate (SZC), on K+ redistribution and excretion in patients remain incompletely understood. We built a fit-for-purpose systems pharmacology model to describe K+ homeostasis in hyperkalemic subjects and capture serum K+ (sK+ ) dynamics in response to acute and chronic administration of SZC. The resulting model describes K+ distribution in the gastrointestinal (GI) tract, blood, and extracellular and intracellular spaces of tissue, renal clearance of K+ , and K+ -SZC binding and excretion in the GI tract. The model, which was fit to time-course sK+ data for individual patients from two clinical trials, accounts for bolus delivery of K+ in meals and oral doses of SZC. The virtual population of patients derived from fitting the model to these trials was then modified to predict the SZC dose-response and inform clinical trial design in two new applications: emergency lowering of sK+ in severe hyperkalemia and prevention of hyperkalemia between dialysis sessions in patients with end-stage chronic kidney disease. In both cases, the model provided novel and useful insight that was borne out by the now completed clinical trials, providing a concrete case study of fit-for-purpose, model-informed drug development after initial approval of a drug.

The Laboratory and Clinical Perspectives of Magnesium Imbalance.

Magnesium (Mg2+) is a predominantly intracellular cation that plays significant roles in various enzymatic, membrane, and structural body functions. As a calcium (Ca2+) antagonist, it is imperative for numerous neuromuscular activities. The imbalance of body Mg2+ concentration leads to clinical manifestations ranging from asymptomatic to severe life-threatening complications. Therefore, the contribution of Mg2+ measurementregarding various laboratory and clinical aspects cannot be ignored. Mg2+ is often described as the forgotten analyte. However, its close relationship with body potassium (K+), Ca2+, and phosphate homeostasis proves that Mg2+ imbalance could co-exist as the root cause or the consequence of other electrolyte disorders. Meanwhile, several preanalytical, analytical, and postanalytical aspects could influence Mg2+ measurement. This review highlights Mg2+ measurement's laboratory and clinical issues and some analyte disturbances associated with its imbalance. Understanding this basis could aid clinicians and laboratory professionals in Mg2+result interpretation and patient management.

Assessment of dietary magnesium intake in the Eastern Province of Saudi Arabia.

Magnesium is an essential element and the most abundant intracellular cation after potassium. This cross-sectional study assessed the average dietary magnesium intake among residents of the Eastern Province of Saudi Arabia. Data was collected using a self-reported validated electronic questionnaire between April 2022 and July 2023. The first part of the survey included demographic data, and the second section comprised 33 items, including a semi-quantitative tool specifically designed to evaluate magnesium intake over the last three months. We included 1065 participants, out of whom 61.1% were women. The predominant age group was 19 - 26 years (56.9%), and most participants (83.3%) reported no comorbidities. The majority (48.5%) had normal weight, 246 (23%) were overweight, and 193 (18.1%) were obese. Most participants had low dietary magnesium intake, ranging from one to five times monthly. There was a positive correlation between age and dietary magnesium consumption. The study highlights a concerning trend of low magnesium intake, representing a risk for various chronic diseases. This trend could be linked to increased consumption of typical diets low in magnesium, such as those high in refined sugars, flour, and processed foods, prevalent among the younger Saudi population.

DNAR-11. NUCLEAR POTASSIUM GOVERNS NUCLEAR ENVELOPE INTEGRITY AND GENOMIC STRUCTURE IN MEDULLOBLASTOMA

Abstract Potassium is the most abundant intracellular cation with crucial functions such as regulating cell proliferation, migration, and differentiation. Potassium flux across cellular membranes is controlled by potassium channels. While the role of cytosolic potassium has been researched for many decades, very little is known about the modulation or significance of potassium in the cell nucleus. Here, we identify potassium channel subunit KCNG1 as a novel regulator of nuclear potassium in medulloblastoma (MB), the most common malignant pediatric brain tumour. Using genetically encoded Förster resonance energy transfer (FRET)-based potassium sensors, we show that KCNG1 regulates nuclear potassium level independently of cytosolic potassium level. KCNG1 knockdown alters the genomic architecture of MB cells by stabilizing G-quadruplex (G4) DNA, inducing DNA damage, and reducing nuclear envelope-associated heterochromatin. Ultimately, KCNG1 deficiency results in nuclear swelling, thereby compromising nuclear envelope integrity and inducing DNA spillage into the cytosol to activate the pro-inflammatory cGAS/STING pathway. Genetic knockdown of KCNG1 mitigates tumour growth and prolongs the survival of mice bearing MB of distinct subgroups. Altogether, our findings reveal that nuclear potassium regulates genomic structure and nuclear envelope integrity and demonstrate that targeting a nuclear potassium channel can be leveraged to activate immunogenic signalling in MB.

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.

The biophysical properties of TRIC-A and TRIC-B and their interactions with RyR2.

Trimeric intracellular cation channels (TRIC-A and TRIC-B) are thought to provide counter-ion currents to enable charge equilibration across the sarco/endoplasmic reticulum (SR) and nuclear membranes. However, there is also evidence that TRIC-A may interact directly with ryanodine receptor type 1 (RyR1) and 2 (RyR2) to alter RyR channel gating. It is therefore possible that the reverse is also true, where the presence of RyR channels is necessary for fully functional TRIC channels. We therefore coexpressed mouse TRIC-A or TRIC-B with mouse RyR2 in HEK293 cells to examine if after incorporating membrane vesicles from these cells into bilayers, the presence of TRIC affects RyR2 function, and to characterize the permeability and gating properties of the TRIC channels. Importantly, we used no purification techniques or detergents to minimize damage to TRIC and RyR2 proteins. We found that both TRIC-A and TRIC-B altered the gating behavior of RyR2 and its response to cytosolic Ca2+ but that TRIC-A exhibited a greater ability to stimulate the opening of RyR2. Fusing membrane vesicles containing TRIC-A or TRIC-B into bilayers caused the appearance of rapidly gating current fluctuations of multiple amplitudes. The reversal potentials of bilayers fused with high numbers of vesicles containing TRIC-A or TRIC-B revealed both Cl- and K+ fluxes, suggesting that TRIC channels are relatively non-selective ion channels. Our results indicate that the physiological roles of TRIC-A and TRIC-B may include direct, complementary regulation of RyR2 gating in addition to the provision of counter-ion currents of both cations and anions.

Beyond Ion Homeostasis: Hypomagnesemia, Transient Receptor Potential Melastatin Channel 7, Mitochondrial Function, and Inflammation.

As the second most abundant intracellular divalent cation, magnesium (Mg2+) is essential for cell functions, such as ATP production, protein/DNA synthesis, protein activity, and mitochondrial function. Mg2+ plays a critical role in heart rhythm, muscle contraction, and blood pressure. A significant decline in Mg2+ intake has been reported in developed countries because of the increased consumption of processed food and filtered/deionized water, which can lead to hypomagnesemia (HypoMg). HypoMg is commonly observed in cardiovascular diseases, such as heart failure, hypertension, arrhythmias, and diabetic cardiomyopathy, and HypoMg is a predictor for cardiovascular and all-cause mortality. On the other hand, Mg2+ supplementation has shown significant therapeutic effects in cardiovascular diseases. Some of the effects of HypoMg have been ascribed to changes in Mg2+ participation in enzyme activity, ATP stabilization, enzyme kinetics, and alterations in Ca2+, Na+, and other cations. In this manuscript, we discuss new insights into the pathogenic mechanisms of HypoMg that surpass previously described effects. HypoMg causes mitochondrial dysfunction, oxidative stress, and inflammation. Many of these effects can be attributed to the HypoMg-induced upregulation of a Mg2+ transporter transient receptor potential melastatin 7 channel (TRMP7) that is also a kinase. An increase in kinase signaling mediated by HypoMg-induced TRPM7 transcriptional upregulation, independently of any change in Mg2+ transport function, likely seems responsible for many of the effects of HypoMg. Therefore, Mg2+ supplementation and TRPM7 kinase inhibition may work to treat the sequelae of HypoMg by preventing increased TRPM7 kinase activity rather than just altering ion homeostasis. Since many diseases are characterized by oxidative stress or inflammation, Mg2+ supplementation and TRPM7 kinase inhibition may have wider implications for other diseases by acting to reduce oxidative stress and inflammation.