• MeSH
• acidóza diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• alkalóza diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• diabetes insipidus diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• draslík metabolismus   MeSH
• poruchy acidobazické rovnováhy * diagnóza   etiologie   klasifikace   MeSH
• sodík metabolismus   MeSH
• vápník metabolismus   MeSH
• vodní a elektrolytová nerovnováha * diagnóza   farmakoterapie   klasifikace   metabolismus   patofyziologie   MeSH
• Publikační typ
• přehledy MeSH

Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. Keywords: Cardiorenal syndrome, Renocardiac syndrome, Volume overload, Sodium retention.

• MeSH
• homeostáza * fyziologie   MeSH
• kardiorenální syndrom * metabolismus   patofyziologie   MeSH
• ledviny metabolismus   patofyziologie   MeSH
• lidé MeSH
• sodík * metabolismus   MeSH
• voda metabolismus   MeSH
• vodní a elektrolytová nerovnováha metabolismus   patofyziologie   MeSH
• vodní a elektrolytová rovnováha * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the objective of discovering new blockers of NaV channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of NaV channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC50. These five alkaloids were then assayed using the Na+ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNaV1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na+ currents elicited by the hNaV1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na+ currents elicited by the hNav1.2 and hNav1.6 channels, with IC50 values below 10 μM. So far, bebeerine is the first BBIQ to have been reported to block NaV channels, with promising therapeutical applications.

• MeSH
• alkaloidy * farmakologie   MeSH
• batrachotoxiny metabolismus   farmakologie   MeSH
• fluorescenční barviva * MeSH
• HEK293 buňky MeSH
• isochinoliny farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• sodík metabolismus   MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Sodium glucose transporter type 2 (SGLT2) molecules are found in proximal tubules of the kidney, and perhaps in the brain or intestine, but rarely in any other tissue. However, their inhibitors, intended to improve diabetes compensation, have many more beneficial effects. They improve kidney and cardiovascular outcomes and decrease mortality. These benefits are not limited to diabetics but were also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in both clinical and experimental studies. There have been numerous excellent reviews, but these were mostly restricted to limited aspects of the knowledge. The aim of this review is to summarize the known experimental and clinical evidence of SGLT2 inhibitors' effects on individual organs (kidney, heart, liver, etc.), as well as the systemic changes that lead to an improvement in clinical outcomes.

• MeSH
• diabetes mellitus 2. typu * farmakoterapie   metabolismus   MeSH
• glifloziny * farmakologie   terapeutické užití   MeSH
• glukosa terapeutické užití   MeSH
• kardiovaskulární systém * metabolismus   MeSH
• lidé MeSH
• sodík metabolismus   MeSH
• transportér 2 pro sodík a glukózu metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Erv14, a conserved cargo receptor of COPII vesicles, helps the proper trafficking of many but not all transporters to the yeast plasma membrane, for example, three out of five alkali-metal-cation transporters in Saccharomyces cerevisiae. Among them, the Nha1 cation/proton antiporter, which participates in cell cation and pH homeostasis, is a large membrane protein (985 aa) possessing a long hydrophilic C-terminus (552 aa) containing six conserved regions (C1-C6) with unknown function. A short Nha1 version, lacking almost the entire C-terminus, still binds to Erv14 but does not need it to be targeted to the plasma membrane. Comparing the localization and function of ScNha1 variants shortened at its C-terminus in cells with or without Erv14 reveals that only ScNha1 versions possessing the complete C5 region are dependent on Erv14. In addition, our broad evolutionary conservation analysis of fungal Na+ /H+ antiporters identified new conserved regions in their C-termini, and our experiments newly show C5 and other, so far unknown, regions of the C-terminus, to be involved in the functionality and substrate specificity of ScNha1. Taken together, our results reveal that also relatively small hydrophilic parts of some yeast membrane proteins underlie their need to interact with the Erv14 cargo receptor.

• MeSH
• antiportéry genetika   metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• COP-vezikuly genetika   metabolismus   MeSH
• endoplazmatické retikulum metabolismus   MeSH
• membránové proteiny metabolismus   fyziologie   MeSH
• proteiny přenášející kationty metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   fyziologie   MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• sodík metabolismus   MeSH
• transport proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The ratio between Na+-Ca2+ exchange current densities in t-tubular and surface membranes of rat ventricular cardiomyocytes (JNaCa-ratio) estimated from electrophysiological data published to date yields strikingly different values between 1.7 and nearly 40. Possible reasons for such divergence were analysed by Monte Carlo simulations assuming both normal and log-normal distribution of the measured data. The confidence intervals CI95 of the mean JNaCa-ratios computed from the reported data showed an overlap of values between 1 and 3, and between 0.3 and 4.3 in the case of normal and log-normal distribution, respectively. Further analyses revealed that the published high values likely result from a large scatter of data due to transmural differences in JNaCa, dispersion of cell membrane capacitances and variability in incomplete detubulation. Taking into account the asymmetric distribution of the measured data, the reduction of mean current densities after detubulation and the substantially smaller CI95 of lower values of the mean JNaCa-ratio, the values between 1.6 and 3.2 may be considered as the most accurate estimates. This implies that 40 to 60% of Na+-Ca2+ exchanger is located at the t-tubular membrane of adult rat ventricular cardiomyocytes.

• MeSH
• kardiomyocyty * metabolismus   MeSH
• krysa rodu rattus MeSH
• pumpa pro výměnu sodíku a vápníku MeSH
• sarkolema metabolismus   MeSH
• sodík metabolismus   MeSH
• srdeční komory metabolismus   MeSH
• vápník * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The sodium/calcium exchanger (NCX) is a unique calcium transport system, generally transporting calcium ions out of the cell in exchange for sodium ions. Nevertheless, under special conditions this transporter can also work in a reverse mode, in which direction of the ion transport is inverted-calcium ions are transported inside the cell and sodium ions are transported out of the cell. To date, three isoforms of the NCX have been identified and characterized in humans. Majority of information about the NCX function comes from isoform 1 (NCX1). Although knowledge about NCX function has evolved rapidly in recent years, little is known about these transport systems in cancer cells. This review aims to summarize current knowledge about NCX functions in individual types of cancer cells.

• MeSH
• invazivní růst nádoru MeSH
• iontový transport MeSH
• lidé MeSH
• nádory metabolismus   MeSH
• pumpa pro výměnu sodíku a vápníku metabolismus   MeSH
• sodík metabolismus   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The G protein-coupled cysteinyl leukotriene receptor CysLT1R mediates inflammatory processes and plays a major role in numerous disorders, including asthma, allergic rhinitis, cardiovascular disease, and cancer. Selective CysLT1R antagonists are widely prescribed as antiasthmatic drugs; however, these drugs demonstrate low effectiveness in some patients and exhibit a variety of side effects. To gain deeper understanding into the functional mechanisms of CysLTRs, we determined the crystal structures of CysLT1R bound to two chemically distinct antagonists, zafirlukast and pranlukast. The structures reveal unique ligand-binding modes and signaling mechanisms, including lateral ligand access to the orthosteric pocket between transmembrane helices TM4 and TM5, an atypical pattern of microswitches, and a distinct four-residue-coordinated sodium site. These results provide important insights and structural templates for rational discovery of safer and more effective drugs.

• MeSH
• antagonisté leukotrienů chemie   metabolismus   MeSH
• antiastmatika chemie   metabolismus   MeSH
• chromony chemie   metabolismus   MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• ligandy MeSH
• receptory leukotrienů chemie   genetika   metabolismus   MeSH
• rekombinantní proteiny biosyntéza   chemie   izolace a purifikace   MeSH
• simulace molekulového dockingu MeSH
• sodík chemie   metabolismus   MeSH
• terciární struktura proteinů MeSH
• tosylové sloučeniny chemie   metabolismus   MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Maintenance of proper intracellular concentrations of monovalent cations, mainly sodium and potassium, is a requirement for survival of any cell. In the budding yeast Saccharomyces cerevisiae, monovalent cation homeostasis is determined by the active extrusion of protons through the Pma1 H+ -ATPase (reviewed in another chapter of this issue), the influx and efflux of these cations through the plasma membrane transporters (reviewed in this chapter), and the sequestration of toxic cations into the vacuoles. Here, we will describe the structure, function, and regulation of the plasma membrane transporters Trk1, Trk2, Tok1, Nha1, and Ena1, which play a key role in maintaining physiological intracellular concentrations of Na+ , K+ , and H+ , both under normal growth conditions and in response to stress.

• MeSH
• buněčná membrána genetika   metabolismus   MeSH
• draslík metabolismus   MeSH
• draslíkové kanály genetika   metabolismus   MeSH
• homeostáza MeSH
• iontový transport MeSH
• kationty jednomocné metabolismus   MeSH
• Na(+)-H(+) antiport genetika   metabolismus   MeSH
• proteiny přenášející kationty genetika   metabolismus   MeSH
• protonové ATPasy MeSH
• regulace genové exprese u hub MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• sodík metabolismus   MeSH
• sodíko-draslíková ATPasa genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Candida glabrata is a haploid yeast that is considered to be an emergent pathogen since it is the second most prevalent cause of candidiasis. Contrary to most yeasts, this species carries only one plasma membrane potassium transporter named CgTrk1. We show in this work that the activity of this transporter is regulated at the posttranslational level, and thus Trk1 contributes to potassium uptake under very different external cation concentrations. In addition to its function in potassium uptake, we report a diversity of physiological effects related to this transporter. CgTRK1 contributes to proper cell size, intracellular pH and membrane-potential homeostasis when expressed in Saccharomyces cerevisiae. Moreover, lithium influx experiments performed both in C. glabrata and S. cerevisiae indicate that the salt tolerance phenotype linked to CgTrk1 can be related to a high capacity to discriminate between potassium and lithium (or sodium) during the transport process. In summary, we show that CgTRK1 exerts a diversity of pleiotropic physiological roles and we propose that the corresponding protein may be an attractive pharmacological target for the development of new antifungal drugs.

• MeSH
• buněčná membrána metabolismus   MeSH
• Candida glabrata genetika   metabolismus   MeSH
• draslík metabolismus   MeSH
• fungální proteiny genetika   metabolismus   MeSH
• homeostáza MeSH
• koncentrace vodíkových iontů MeSH
• proteiny přenášející kationty genetika   metabolismus   MeSH
• regulace genové exprese u hub MeSH
• sodík metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH