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1.
Int J Mol Sci ; 23(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36077010

RESUMO

Cystic fibrosis (CF) is caused by mutations in the gene encoding of the cystic fibrosis transmembrane conductance regulator (CFTR), an anion-selective plasma membrane channel that mainly regulates chloride transport in a variety of epithelia. More than 2000 mutations, most of which presumed to be disease-relevant, have been identified in the CFTR gene. The single CFTR mutation F508del (deletion of phenylalanine in position 508) is present in about 90% of global CF patients in at least one allele. F508del is responsible for the defective folding and processing of CFTR, failing to traffic to the plasma membrane and undergoing premature degradation via the ubiquitin-proteasome system. CFTR is subjected to different post-translational modifications (PTMs), and the possibility to modulate these PTMs has been suggested as a potential therapeutic strategy for the functional recovery of the disease-associated mutants. Recently, the PTM mapping of CFTR has identified some lysine residues that may undergo methylation or ubiquitination, suggesting a competition between these two PTMs. Our work hypothesis moves from the idea that favors methylation over ubiquitination, e.g., inhibiting demethylation could be a successful strategy for preventing the premature degradation of unstable CFTR mutants. Here, by using a siRNA library against all the human demethylases, we identified the enzymes whose downregulation increases F508del-CFTR stability and channel function. Our results show that KDM2A and KDM3B downregulation increases the stability of F508del-CFTR and boosts the functional rescue of the channel induced by CFTR correctors.


Assuntos
Fibrose Cística , Proteínas F-Box , Membrana Celular/metabolismo , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Proteínas F-Box/genética , Humanos , Transporte de Íons , Histona Desmetilases com o Domínio Jumonji/metabolismo , Mutação
2.
Elife ; 112022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36065640

RESUMO

Rhodopsins convert light into signals and energy in animals and microbes. Heliorhodopsins (HeRs), a recently discovered new rhodopsin family, are widely present in archaea, bacteria, unicellular eukaryotes, and giant viruses, but their function remains unknown. Here, we report that a viral HeR from Emiliania huxleyi virus 202 (V2HeR3) is a light-activated proton transporter. V2HeR3 absorbs blue-green light, and the active intermediate contains the deprotonated retinal Schiff base. Site-directed mutagenesis study revealed that E191 in TM6 constitutes the gate together with the retinal Schiff base. E205 and E215 form a PAG of the Schiff base, and mutations at these positions converted the protein into an outward proton pump. Three environmental viral HeRs from the same group as well as a more distantly related HeR exhibited similar proton-transport activity, indicating that HeR functions might be diverse similarly to type-1 microbial rhodopsins. Some strains of E. huxleyi contain one HeR that is related to the viral HeRs, while its viruses EhV-201 and EhV-202 contain two and three HeRs, respectively. Except for V2HeR3 from EhV-202, none of these proteins exhibit ion transport activity. Thus, when expressed in the E. huxleyi cell membranes, only V2HeR3 has the potential to depolarize the host cells by light, possibly to overcome the host defense mechanisms or to prevent superinfection. The neuronal activity generated by V2HeR3 suggests that it can potentially be used as an optogenetic tool, similarly to type-1 microbial rhodopsins.


Assuntos
Vírus Gigantes , Prótons , Animais , Transporte de Íons , Rodopsina/genética , Rodopsinas Microbianas/genética , Bases de Schiff
3.
Nat Commun ; 13(1): 5270, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085139

RESUMO

Ion-transport mechanisms evolve by changing ion-selectivity, such as switching from Na+ to H+ selectivity in secondary-active transporters or P-type-ATPases. Here we study primary-active transport via P-type ATPases using functional and structural analyses to demonstrate that four simultaneous residue substitutions transform the non-gastric H+/K+ pump, a strict H+-dependent electroneutral P-type ATPase, into a bona fide Na+-dependent electrogenic Na+/K+ pump. Conversion of a H+-dependent primary-active transporter into a Na+-dependent one provides a prototype for similar studies of ion-transport proteins. Moreover, we solve the structures of the wild-type non-gastric H+/K+ pump, a suitable drug target to treat cystic fibrosis, and of its Na+/K+ pump-mimicking mutant in two major conformations, providing insight on how Na+ binding drives a concerted mechanism leading to Na+/K+ pump phosphorylation.


Assuntos
Fibrose Cística , ATPases do Tipo-P , Humanos , Transporte de Íons , Íons , Mutação de Sentido Incorreto
4.
Sci Signal ; 15(752): eabl5848, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36126118

RESUMO

Goblet cells in the small intestinal crypts contain large numbers of mucin granules that are rapidly discharged to clean bacteria from the crypt. Because acetylcholine released by neuronal and nonneuronal cells controls many aspects of intestinal epithelial function, we used tissue explants and organoids to investigate the response of the small intestinal crypt to cholinergic stimulation. The activation of muscarinic acetylcholine receptors initiated a coordinated and rapid emptying of crypt goblet cells that flushed the crypt contents into the intestinal lumen. Cholinergic stimulation induced an expansion of the granule contents followed by intracellular rupture of the mucin granules. The mucus expanded intracellularly before the rupture of the goblet cell apical membrane and continued to expand after its release into the crypt lumen. The goblet cells recovered from membrane rupture and replenished their stores of mucin granules. Mucus secretion from the goblet cells depended on Ca2+ signaling and the expansion of the mucus in the crypt depended on gap junctions and on ion and water transport by enterocytes adjacent to the goblet cells. This distinctive mode of mucus secretion, which we refer to as "expanding secretion," efficiently cleans the small intestine crypt through coordinated mucus, ion, and fluid secretion by goblet cells and enterocytes.


Assuntos
Enterócitos , Células Caliciformes , Acetilcolina/metabolismo , Acetilcolina/farmacologia , Colinérgicos/metabolismo , Enterócitos/metabolismo , Mucosa Intestinal/metabolismo , Transporte de Íons , Mucinas/metabolismo , Muco/metabolismo , Água/metabolismo
5.
Org Biomol Chem ; 20(35): 7056-7066, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-35993191

RESUMO

Stimuli responsive anion transport is becoming an important aspect of supramolecular anion recognition chemistry. Herein, we report the synthesis of a family of anion receptors that incorporate a new anion binding motif, amidosquaramides. We show using experimental and computational methods that these receptors have pKa values close to physiological pH but also display intramolecular H-bonding interactions that affect anion recognition. Moreover, moderate activity in a Cl-/NO3- exchange assay is observed at physiological pH that can be effectively 'switched on' when repeated under acidic conditions. The reported findings provide synthetic methods that can be used for the construction of more complex squaramide based anion receptors and also provide insight into the importance of conformational analysis when considering receptor design.


Assuntos
Proteínas de Transporte , Ânions/química , Concentração de Íons de Hidrogênio , Transporte de Íons
6.
Langmuir ; 38(36): 11022-11032, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36044592

RESUMO

The feasibility of detecting a trace concentration of multivalent ions based on the ionic current rectification (ICR) of a nanopore when impurity ions might present is assessed. Adopting a bullet-shaped nanopore surface modified with tannic acid as an example, the detection of trace concentrations of Cu2+ (target ion) when Fe3+ (impurity) is present with K+ as background ions under various conditions is simulated. In particular, the influence of the reaction order of the association of target ions and tannic acid on the nanopore performance is examined. We show that the lower the background concentration the better the detection performance. For the examined background concentrations of 1, 10, 100, and 1000 mM, the optimal detection ranges are [0.5, 1000 µM] and [1, 1000 nM] for Cu2+ and Fe3+, respectively. The detection limits, 0.5 µM for Cu2+ and 1 nM for Fe3+, are lower than those that can be obtained from conventional instruments, suggesting the potential of applying the present nanopore-based approach. In addition, we also consider the presence of multiple ions, which can occur, for example, in detecting Cu2+ (target ion) when Fe3+ (impurity) might present or vice versa with K+ as background ions. The competitive adsorption of these three kinds of ions can yield complicated ICR behaviors.


Assuntos
Nanoporos , Adsorção , Transporte de Íons , Íons , Taninos
7.
Int J Mol Sci ; 23(16)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36012415

RESUMO

A facile methodology system for synthesizing solid polymer electrolytes (SPEs) based on methylcellulose, dextran, lithium perchlorate (as ionic sources), and glycerol (such as a plasticizer) (MC:Dex:LiClO4:Glycerol) has been implemented. Fourier transform infrared spectroscopy (FTIR) and two imperative electrochemical techniques, including linear sweep voltammetry (LSV) and electrical impedance spectroscopy (EIS), were performed on the films to analyze their structural and electrical properties. The FTIR spectra verify the interactions between the electrolyte components. Following this, a further calculation was performed to determine free ions (FI) and contact ion pairs (CIP) from the deconvolution of the peak associated with the anion. It is verified that the electrolyte containing the highest amount of glycerol plasticizer (MDLG3) has shown a maximum conductivity of 1.45 × 10-3 S cm-1. Moreover, for other transport parameters, the mobility (µ), number density (n), and diffusion coefficient (D) of ions were enhanced effectively. The transference number measurement (TNM) of electrons (tel) was 0.024 and 0.976 corresponding to ions (tion). One of the prepared samples (MDLG3) had 3.0 V as the voltage stability of the electrolyte.


Assuntos
Glicerol , Plastificantes , Biopolímeros/química , Eletrólitos/química , Transporte de Íons , Íons , Lítio
8.
Int J Mol Sci ; 23(16)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36012428

RESUMO

Na+/H+ exchangers are essential for Na+ and pH homeostasis in all organisms. Human Na+/H+ exchangers are of high medical interest, and insights into their structure and function are aided by the investigation of prokaryotic homologues. Most prokaryotic Na+/H+ exchangers belong to either the Cation/Proton Antiporter (CPA) superfamily, the Ion Transport (IT) superfamily, or the Na+-translocating Mrp transporter superfamily. Several structures have been solved so far for CPA and Mrp members, but none for the IT members. NhaA from E. coli has served as the prototype of Na+/H+ exchangers due to the high amount of structural and functional data available. Recent structures from other CPA exchangers, together with diverse functional information, have allowed elucidation of some common working principles shared by Na+/H+ exchangers from different families, such as the type of residues involved in the substrate binding and even a simple mechanism sufficient to explain the pH regulation in the CPA and IT superfamilies. Here, we review several aspects of prokaryotic Na+/H+ exchanger structure and function, discussing the similarities and differences between different transporters, with a focus on the CPA and IT exchangers. We also discuss the proposed transport mechanisms for Na+/H+ exchangers that explain their highly pH-regulated activity profile.


Assuntos
Proteínas de Escherichia coli , Trocadores de Sódio-Hidrogênio , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Transporte de Íons/fisiologia , Sódio/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo
10.
Small ; 18(35): e2203104, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35931455

RESUMO

Smart modulation of bioelectric signals is of great significance for the development of brain-computer interfaces, bio-computers, and other technologies. The regulation and transmission of bioelectrical signals are realized through the synergistic action of various ion channels in organisms. The bionic nanochannels, which have similar physiological working environment and ion rectification as their biological counterparts, can be used to construct ion rectifier bridges to modulate the bioelectric signals. Here, the artificial smart ionic rectifier bridge with light response is constructed by anodic aluminum oxide (AAO)/poly (spiropyran acrylate) (PSP) nanochannels. The output ion current of the rectifier bridge can be switched between "ON" and "OFF" states by irradiation with UV and visible (Vis) light, and the conversion efficiency (η) of the system in "ON" state is ≈70.5%. The controllable modulation of brain wave-like signal can be realized by ionic rectifier bridge. The ion transport properties and processes of ion rectifier bridges are explained using theoretical calculations based on Poisson-Nernst-Planck (PNP) equations. These findings have significant implications for the understanding of the intelligent ionic circuit and combination of artificial smart ionic channels to organisms, which provide new avenues for development of intelligent ion devices.


Assuntos
Ondas Encefálicas , Canais Iônicos , Transporte de Íons , Íons , Luz
11.
Int J Mol Sci ; 23(16)2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-36012718

RESUMO

The non-linear voltage-dependent hysteresis (Hys(V)) of voltage-gated ionic currents can be robustly activated by the isosceles-triangular ramp voltage (Vramp) through digital-to-analog conversion. Perturbations on this Hys(V) behavior play a role in regulating membrane excitability in different excitable cells. A variety of small molecules may influence the strength of Hys(V) in different types of ionic currents elicited by long-lasting triangular Vramp. Pirfenidone, an anti-fibrotic drug, decreased the magnitude of Ih's Hys(V) activated by triangular Vramp, while dexmedetomidine, an agonist of α2-adrenoceptors, effectively suppressed Ih as well as diminished the Hys(V) strength of Ih. Oxaliplatin, a platinum-based anti-neoplastic drug, was noted to enhance the Ih's Hys(V) strength, which is thought to be linked to the occurrence of neuropathic pain, while honokiol, a hydroxylated biphenyl compound, decreased Ih's Hys(V). Cell exposure to lutein, a xanthophyll carotenoid, resulted in a reduction of Ih's Hys(V) magnitude. Moreover, with cell exposure to UCL-2077, SM-102, isoplumbagin, or plumbagin, the Hys(V) strength of erg-mediated K+ current activated by triangular Vramp was effectively diminished, whereas the presence of either remdesivir or QO-58 respectively decreased or increased Hys(V) magnitude of M-type K+ current. Zingerone, a methoxyphenol, was found to attenuate Hys(V) (with low- and high-threshold loops) of L-type Ca2+ current induced by long-lasting triangular Vramp. The Hys(V) properties of persistent Na+ current (INa(P)) evoked by triangular Vramp were characterized by a figure-of-eight (i.e., ∞) configuration with two distinct loops (i.e., low- and high-threshold loops). The presence of either tefluthrin, a pyrethroid insecticide, or t-butyl hydroperoxide, an oxidant, enhanced the Hys(V) strength of INa(P). However, further addition of dapagliflozin can reverse their augmenting effects in the Hys(V) magnitude of the current. Furthermore, the addition of esaxerenone, mirogabalin, or dapagliflozin was effective in inhibiting the strength of INa(P). Taken together, the observed perturbations by these small-molecule modulators on Hys(V) strength in different types of ionic currents evoked during triangular Vramp are expected to influence the functional activities (e.g., electrical behaviors) of different excitable cells in vitro or in vivo.


Assuntos
Amino Álcoois , Caprilatos , Transporte de Íons , Sódio
12.
Am J Physiol Lung Cell Mol Physiol ; 323(3): L240-L250, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35819839

RESUMO

The balance of gas exchange and lung ventilation is essential for the maintenance of body homeostasis. There are many ion channels and transporters in respiratory epithelial cells, including epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator, and some transporters. These ion channels/transporters maintain the capacity of liquid layer on the surface of respiratory epithelial cells and provide an immune barrier for the respiratory system to clear off foreign pathogens. However, in some harmful external environments and/or pathological conditions, the respiratory epithelium is prone to hypoxia, which would destroy the ion transport function of the epithelium and unbalance the homeostasis of internal environment, triggering a series of pathological reactions. Many respiratory diseases associated with hypoxia manifest an increased expression of hypoxia-inducible factor-1, which mediates the integrity of the epithelial barrier and affects epithelial ion transport function. It is important to study the relationship between hypoxia and ion transport function, whereas the mechanism of hypoxia-induced ion transport dysfunction in respiratory diseases is not clear. This review focuses on the relationship between hypoxia and respiratory diseases, as well as dysfunction of ion transport and tight junctions in respiratory epithelial cells under hypoxia.


Assuntos
Transtornos Respiratórios , ATPase Trocadora de Sódio-Potássio , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Canais Epiteliais de Sódio/metabolismo , Humanos , Hipóxia/metabolismo , Transporte de Íons , Transtornos Respiratórios/metabolismo , Mucosa Respiratória/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
13.
J Clin Invest ; 132(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35900863

RESUMO

The vast majority of people with cystic fibrosis (CF) are now eligible for CF transmembrane regulator (CFTR) modulator therapy. The remaining individuals with CF harbor premature termination codons (PTCs) or rare CFTR variants with limited treatment options. Although the clinical modulator response can be reliably predicted using primary airway epithelial cells, primary cells carrying rare CFTR variants are scarce. To overcome this obstacle, cell lines can be created by overexpression of mouse Bmi-1 and human TERT (hTERT). Using this approach, we developed 2 non-CF and 6 CF airway epithelial cell lines, 3 of which were homozygous for the W1282X PTC variant. The Bmi-1/hTERT cell lines recapitulated primary cell morphology and ion transport function. The 2 F508del-CFTR cell lines responded robustly to CFTR modulators, which was mirrored in the parent primary cells and in the cell donors' clinical response. Cereblon E3 ligase modulators targeting eukaryotic release factor 3a (eRF3a) rescued W1282X-CFTR function to approximately 20% of WT levels and, when paired with G418, rescued G542X-CFTR function to approximately 50% of WT levels. Intriguingly, eRF3a degraders also diminished epithelial sodium channel (ENaC) function. These studies demonstrate that Bmi-1/hTERT cell lines faithfully mirrored primary cell responses to CFTR modulators and illustrate a therapeutic approach to rescue CFTR nonsense mutations.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Animais , Linhagem Celular , Códon sem Sentido , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Humanos , Transporte de Íons/genética , Camundongos , Mutação
14.
Proc Natl Acad Sci U S A ; 119(30): e2113963119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858440

RESUMO

Transporters belonging to the Resistance-Nodulation-cell Division (RND) superfamily of proteins such as Mycobacterium tuberculosis MmpL3 and its analogs are the focus of intense investigations due to their importance in the physiology of Corynebacterium-Mycobacterium-Nocardia species and antimycobacterial drug discovery. These transporters deliver trehalose monomycolates, the precursors of major lipids of the outer membrane, to the periplasm by a proton motive force-dependent mechanism. In this study, we successfully purified, from native membranes, the full-length and the C-terminal truncated M. tuberculosis MmpL3 and Corynebacterium glutamicum CmpL1 proteins and reconstituted them into proteoliposomes. We also generated a series of substrate mimics and inhibitors specific to these transporters, analyzed their activities in the reconstituted proteoliposomes, and carried out molecular dynamics simulations of the model MmpL3 transporter at different pH. We found that all reconstituted proteins facilitate proton translocation across a phospholipid bilayer, but MmpL3 and CmpL1 differ dramatically in their responses to pH and interactions with substrate mimics and indole-2-carboxamide inhibitors. Our results further suggest that some inhibitors abolish the transport activity of MmpL3 and CmpL1 by inhibition of proton translocation.


Assuntos
Proteínas de Bactérias , Proteínas de Membrana Transportadoras , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Corynebacterium , Transporte de Íons , Bicamadas Lipídicas/química , Proteínas de Membrana Transportadoras/química , Ácidos Micólicos/metabolismo , Prótons , Especificidade por Substrato
15.
J Phys Chem B ; 126(30): 5689-5694, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35867912

RESUMO

Ion current rectification is highly reported in aqueous electrochemical systems and sensors but lacks exploration in organic systems due to the additional complexity introduced by non-aqueous solvents. Herein, a detailed study on ion current rectification with highly polar and mildly polar aprotic organic solvents as a function of tetraethylammonium tetrafluoroborate supporting electrolyte concentration is presented. To explain our experimental results, we introduce a previously unreported phenomenon: the formation of a double-junction diode within the nanopore that arises due to a complex interplay between ion and solvent enrichment effects. Finite element simulations are used to explore this phenomenon and the subsequent effect on the rectifying behavior of conical quartz nanopores.


Assuntos
Nanoporos , Eletrólitos , Transporte de Íons , Solventes
16.
Curr Opin Nephrol Hypertens ; 31(5): 479-485, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35894283

RESUMO

PURPOSE OF REVIEW: Kir5.1 interacts with Kir4.2 in proximal tubule and with Kir4.1 in distal convoluted tubule (DCT), connecting tubule (CNT) and cortical collecting duct (CCD) to form basolateral-K+-channels. Kir4.2/Kir5.1 and Kir4.1/Kir5.1 play an important role in regulating Na+/HCO3--transport of the proximal tubule and Na+/K+ -transport in the DCT/CNT/CCD. The main focus of this review is to provide an overview of the recent development in the field regarding the role of Kir5.1 regulating renal electrolyte transport in the proximal tubule and DCT. RECENT FINDINGS: Loss-of-function-mutations of KCNJ16 cause a new form of tubulopathy, characterized by hypokalaemia, Na+-wasting, acid-base-imbalance and metabolic-acidosis. Abnormal bicarbonate transport induced by loss-of-function of KCNJ16-mutants is recapitulated in Kir4.2-knockout-(Kir4.2 KO) mice. Deletion of Kir5.1 also abolishes the effect of dietary Na+ and K+-intakes on the basolateral membrane voltage and NCC expression/activity. Long-term high-salt intake or high-K+-intake causes hyperkalaemic in Kir5.1-deficient mice. SUMMARY: Kir4.2/Kir5.1 activity in the proximal tubule plays a key role in regulating Na+, K+ and bicarbonate-transport through regulating electrogenic-Na+-bicarbonate-cotransporter-(NBCe1) and type 3-Na+/H+-exchanger-(NHE3). Kir4.1/Kir5.1 activity of the DCT plays a critical role in mediating the effect of dietary-K+ and Na+-intakes on NCC activity/expression. As NCC determines the Na+ delivery rate to the aldosterone-sensitive distal nephron (ASDN), defective regulation of NCC during high-salt and high-K+ compromises renal K+ excretion and K+ homeostasis.


Assuntos
Canais de Potássio Corretores do Fluxo de Internalização , Animais , Bicarbonatos/metabolismo , Humanos , Transporte de Íons/fisiologia , Túbulos Renais/metabolismo , Túbulos Renais Distais/metabolismo , Camundongos , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Sódio/metabolismo
17.
Sci Rep ; 12(1): 12170, 2022 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-35842540

RESUMO

Membrane technology with advantages such as reduced energy consumption due to no phase change, low volume and high mass transfer, high separation efficiency for solution solutions, straightforward design of membranes, and ease of use on industrial scales are different from other separation methods. There are various methods such as liquid-liquid extraction, adsorption, precipitation, and membrane processes to separate contaminants from an aqueous solution. The liquid membrane technique provides a practical and straightforward separation method for metal ions as an advanced solvent extraction technique. Stabilized liquid membranes require less solvent consumption, lower cost, and more effortless mass transfer due to their thinner thickness than other liquid membrane techniques. The influence of the electrostatic properties, derived from the electrical field, on the ionic transport rate and extraction recovery, in flat sheet supported liquid membrane (FSLM) and electro flat sheet supported liquid membrane (EFSLM) were numerically investigated. Both FSLM and EFSLM modes of operation, in terms of implementing electrostatic, were considered. Through adopting a numerical approach, Poisson-Nernst-Planck, and Navier-Stokes equations were solved at unsteady-state conditions by considering different values of permittivity, diffusivity, and viscosity for the presence of electrical force and stirrer, respectively. The most important result of this study is that under similar conditions, by increasing the applied voltage, the extraction recovery increased. For instance, at EFSLM mode, by increasing the applied voltage from [Formula: see text] to [Formula: see text], the extraction recovery increased from [Formula: see text] to [Formula: see text]. Furthermore, it was also observed that the presence of nanoparticles has significant effects on the performance of the SLM system.


Assuntos
Eletricidade Estática , Simulação por Computador , Transporte de Íons , Membranas , Solventes
18.
Int J Mol Sci ; 23(13)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35806190

RESUMO

Lutein (ß,ε-carotene-3,3'-diol), a xanthophyll carotenoid, is found in high concentrations in the macula of the human retina. It has been recognized to exert potential effectiveness in antioxidative and anti-inflammatory properties. However, whether and how its modifications on varying types of plasmalemmal ionic currents occur in electrically excitable cells remain incompletely answered. The current hypothesis is that lutein produces any direct adjustments on ionic currents (e.g., hyperpolarization-activated cation current, Ih [or funny current, If]). In the present study, GH3-cell exposure to lutein resulted in a time-, state- and concentration-dependent reduction in Ih amplitude with an IC50 value of 4.1 µM. There was a hyperpolarizing shift along the voltage axis in the steady-state activation curve of Ih in the presence of this compound, despite being void of changes in the gating charge of the curve. Under continued exposure to lutein (3 µM), further addition of oxaliplatin (10 µM) or ivabradine (3 µM) could be effective at either reversing or further decreasing lutein-induced suppression of hyperpolarization-evoked Ih, respectively. The voltage-dependent anti-clockwise hysteresis of Ih responding to long-lasting inverted isosceles-triangular ramp concentration-dependently became diminished by adding this compound. However, the addition of 10 µM lutein caused a mild but significant suppression in the amplitude of erg-mediated or A-type K+ currents. Under current-clamp potential recordings, the sag potential evoked by long-lasting hyperpolarizing current stimulus was reduced under cell exposure to lutein. Altogether, findings from the current observations enabled us to reflect that during cell exposure to lutein used at pharmacologically achievable concentrations, lutein-perturbed inhibition of Ih would be an ionic mechanism underlying its changes in membrane excitability.


Assuntos
Carotenoides , Luteína , Cátions/farmacologia , Humanos , Transporte de Íons , Luteína/farmacologia , Xantofilas/farmacologia
19.
Sci Adv ; 8(28): eabn4331, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35857505

RESUMO

Zinc is essential for all organisms and yet detrimental at elevated levels. Hence, homeostasis of this metal is tightly regulated. The Zrt/Irt-like proteins (ZIPs) represent the only zinc importers in metazoans. Mutations in human ZIPs cause serious disorders, but the mechanism by which ZIPs transfer zinc remains elusive. Hitherto, structural information is only available for a model member, BbZIP, and as a single, ion-bound conformation, precluding mechanistic insights. Here, we elucidate an inward-open metal-free BbZIP structure, differing substantially in the relative positions of the two separate domains of ZIPs. With accompanying coevolutional analyses, mutagenesis, and uptake assays, the data point to an elevator-type transport mechanism, likely shared within the ZIP family, unifying earlier functional data. Moreover, the structure reveals a previously unknown ninth transmembrane segment that is important for activity in vivo. Our findings outline the mechanistic principles governing ZIP-protein transport and enhance the molecular understanding of ZIP-related disorders.


Assuntos
Proteínas de Transporte de Cátions , Zinco , Transporte Biológico , Proteínas de Transporte de Cátions/metabolismo , Humanos , Transporte de Íons , Metais/metabolismo , Zinco/metabolismo
20.
Pflugers Arch ; 474(8): 869-884, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35895103

RESUMO

Regulated Na+ transport in the distal nephron is of fundamental importance to fluid and electrolyte homeostasis. Further upstream, Na+ is the principal driver of secondary active transport of numerous organic and inorganic solutes. In the distal nephron, Na+ continues to play a central role in controlling the body levels and concentrations of a more select group of ions, including K+, Ca++, Mg++, Cl-, and HCO3-, as well as water. Also, of paramount importance are transport mechanisms aimed at controlling the total level of Na+ itself in the body, as well as its concentrations in intracellular and extracellular compartments. Over the last several decades, the transporters involved in moving Na+ in the distal nephron, and directly or indirectly coupling its movement to that of other ions have been identified, and their interrelationships brought into focus. Just as importantly, the signaling systems and their components-kinases, ubiquitin ligases, phosphatases, transcription factors, and others-have also been identified and many of their actions elucidated. This review will touch on selected aspects of ion transport regulation, and its impact on fluid and electrolyte homeostasis. A particular focus will be on emerging evidence for site-specific regulation of the epithelial sodium channel (ENaC) and its role in both Na+ and K+ homeostasis. In this context, the critical regulatory roles of aldosterone, the mineralocorticoid receptor (MR), and the kinases SGK1 and mTORC2 will be highlighted. This includes a discussion of the newly established concept that local K+ concentrations are involved in the reciprocal regulation of Na+-Cl- cotransporter (NCC) and ENaC activity to adjust renal K+ secretion to dietary intake.


Assuntos
Canais Epiteliais de Sódio , Túbulos Renais Distais , Aldosterona/metabolismo , Eletrólitos/metabolismo , Canais Epiteliais de Sódio/metabolismo , Homeostase , Transporte de Íons , Túbulos Renais Distais/metabolismo , Sódio/metabolismo , Membro 3 da Família 12 de Carreador de Soluto/metabolismo
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