Cation Fluxes Research Articles

Zinc alleviates cadmium toxicity by modulating photosynthesis, ROS homeostasis, and cation flux kinetics in rice

Understanding of cadmium (Cd) uptake mechanism and development of lower Cd crop genotypes are crucial for combating its phytotoxicity and meeting 70% increase in food demand by 2050. Bio-accumulation of Cd continuously challenges quality of life specifically in regions without adequate environmental planning. Here, we investigated the mechanisms operating in Cd tolerance of two rice genotypes (Heizhan-43 and Yinni-801). Damage to chlorophyll contents and PSII, histochemical staining and quantification of reactive oxygen species (ROS), cell viability and osmolyte accumulation were studied to decipher the interactions between Cd and zinc (Zn) by applying two Cd and two Zn levels (alone as well as combined). Cd2+ and Ca2+ fluxes were also measured by employing sole Cd100 (100 μmol L−1) and Zn50 (50 μmol L−1), and their combination with microelectrode ion flux estimation (MIFE) technique. Cd toxicity substantially reduced chlorophyll contents and maximal photochemical efficiency (Fv/Fm) compared to control plants. Zn supplementation reverted the Cd-induced toxicity by augmenting osmoprotectants and interfering with ROS homeostasis under combined treatments, particularly in Yinni-801 genotype. Fluorescence microscopy indicated a unique pattern of live and dead root cells, depicting more damage with Cd10, Cd15 and Cd15+Zn50. Our results confer that Cd2+ impairs the uptake of Ca2+ whereas, Zn not only competes with Cd2+ but also Ca2+, thereby modifying ion homeostasis in rice plants. This study suggests that exogenous application of Zn is beneficial for rice plants in ameliorating Cd toxicity in a genotype and dose dependent manner by minimizing ROS generation and suppressing collective oxidative damage. The observations confer that Yinni-801 performed better than Heizhan-43 genotype mainly under combined Zn treatments with low-Cd, presenting Zn fortification as a solution to increase rice production.

Mitigating nutrient accumulation with microalgal growth towards enhanced nutrient removal and biomass production in an osmotic photobioreactor

Forward osmosis (FO) has great potential for low energy consumption wastewater reuse provided there is no requirement for draw solutes (DS) regeneration. Reverse solute flux (RSF) can lead to DS build-up in the feed solution. This remains a key challenge because it can cause significant water flux reduction and lead to additional water quality problems. Herein, an osmotic photobioreactor (OsPBR) system was developed to employ fast-growing microalgae to consume the RSF nutrients. Diammonium phosphate (DAP) was used as a fertilizer DS, and algal biomass was a byproduct. The addition of microalgae into the OsPBR proved to maintain water flux while reducing the concentrations of NH4+-N, PO43--P and chemical oxygen demand (COD) in the OsPBR feed solution by 44.4%, 85.6%, and 77.5%, respectively. Due to the forward cation flux and precipitation, intermittent supplements of K+, Mg2+, Ca2+, and SO42− salts further stimulated algal growth and culture densities by 58.7%. With an optimal hydraulic retention time (HRT) of 3.33 d, the OsPBR overcame NH4+-N overloading and stabilized key nutrients NH4+-N at ∼ 2.0 mg L−1, PO43--P < 0.6 mg L−1, and COD < 30 mg L−1. A moderate nitrogen reduction stress resulted in a high carbohydrate content (51.3 ± 0.1%) among microalgal cells. A solids retention time (SRT) of 17.82 d was found to increase high-density microalgae by 3-fold with a high yield of both lipids (9.07 g m−3 d−1) and carbohydrates (16.66 g m−3 d−1). This study encourages further exploration of the OsPBR technology for simultaneous recovery of high-quality water and production of algal biomass for value-added products.

A model for evaluating continental chemical weathering from riverine transports of dissolved major elements at a global scale

This study presents a process-based-empirical model for the assessment of ionic fluxes derived from chemical weathering of rocks (ICWR) at a global scale. The equations are designed and the parameters fitted using riverine transport of dissolved major ions Ca2+, Mg2+, K+, Na+, Cl−, SO42−, and alkalinity at a global scale by combining point sampling analysis with spatial descriptions of hydrology, climate, topography, lithology and soil variables such as mineral composition and regolith thickness. Different configurations of the model are considered and the results show that the previously reported “soil shielding” effect on chemical weathering (CW) of rocks presents different values for each of the ions considered. Overall, there is good agreement between median and ranges in observed and simulated data, but further analysis is required to downscale the model to catchment scale. Application to the global scale provides the first global ICWR map, resulting in an average cationic flux derived from chemical weathering of 734·106 Mg·y−1, where 58% is Ca2+, 15% is Mg2+, 24% is Na+ and 3% is K+, and an average anionic flux derived from chemical weathering of 2640·106 Mg·y−1, where 74% is alkalinity, 18% is SO42−, and 8% is Cl−. Hyperactive and hotspot areas are elucidated and compared between ions.

Competitive Counterflow (CCF) To Distinguish Between Transported And Non‐Transported Inhibitors Of MATE1 and MATE2‐K

The MATEs (hMATE1 &amp; hMATE‐2K) are membrane proteins expressed in the apical membrane of renal proximal tubule cells that mediate the flux of organic cations into the filtrate. In this study we set to test CCF as a method to identify substrates of pharmacological interest for both MATEs.We first determined IC50 values for inhibition of MPP transport into CHO cells that stably expressed either MATE1 or MATE2‐K for several clinically important compounds: Amlodipine (IC50= 7‐6 μM), Atenolol (10‐4 μM), Dofetilidae (4‐0.8 μM), Entecavir (302‐140 μM), Lamivudine (336‐53 μM), Omeprazole (53‐8 μM), Propranolol, (16‐5 μM) and Trimethoprim (6‐0.4 μM). For CCF, cells were exposed to ~12 nM [3H]MPP for 40 min, sufficient to reach steady state. At time 0, the medium was removed and replaced with medium containing either ~12 nM [3H]MPP (control) or ~12 nM [3H]MPP plus one of the test compounds, or a known MATE substrate (e.g., Metformin); PAH (1mM) was used as a known non‐transported compound. After an additional 5 min incubation, radiolabeled MPP remaining in the cells was determined. If the extracellular test compound was transported, the associated turnover of the transporter should result in net loss of labeled MPP from the cells. Each test was performed (in sextuplicate) in 2–3 separate experiments.Whereas exposure to 1mM PAH resulted in no loss of MPP from the cells (which was distributed to steady state), exposure to metformin resulted in net loss of radiolabeled substrate (70%). Of the test compounds, Atenolol, Amlodipine &amp; Lamivudine supported a net loss of [3H]MPP (70‐30%) from both MATE1 &amp; MATE2K‐expressing cells, whereas Entecavir reduced total accumulation of MPP only for MATE2K expressing cells. There was no loss (or gain) of MPP induced by Dofetilidae, Propranolol or Omeprazole, suggesting they are non‐transported inhibitors for both MATEs.These data support the conclusion that the method of CCF is applicable for identification of MATE substrates, and identified a difference in the selectivity profile of hMATE1 &amp; hMATE2K.Support or Funding InformationSupported by NIH Award 5R01GM129777

Pathophysiology and recent therapeutic insights of sickle cell disease.

Sickle cell disease (SCD) is an autosomal recessive blood disorder which occurs due to point mutation in the β-globin chain of hemoglobin. Since the past decades, various therapies have been put forth, which are based on obstructing pathophysiological mechanisms of SCD including inhibition of Gardos channel and cation fluxes which in turn prevents sickle erythrocyte destruction and dehydration. The pharmacological approaches are based on the mechanism of reactivating γ-globin expression by utilizing fetal hemoglobin (HbF)-inducing drugs such as hydroxyurea. In SCD, gene therapy could be considered as a promising tool which involves modifying mutation at the gene-specific target by either promoting insertion or deletion of globins. Although there are various therapies emerged so far in the treatment of SCD, many of them have faced a major setback in most of developing countries in terms of cost, unavailability of expertise, and suitable donor. Therefore, in addition to pathophysiological aspects, this review will discuss new advancements and approaches made in the therapeutic domain of SCD including a viewpoint of modulating hemoglobin in SCD by the intervention of probiotics.

Weak impact of landscape parameters and rock lithology on Mg isotope composition of the Yenisey River and its tributaries

Constraining the mechanisms controlling the riverine flux of major cations and their isotopes including that of Mg to the World Ocean is one of the challenges in Earth surface isotope geochemistry. In an attempt to identify the main factors affecting the Mg isotopic composition of large rivers including vegetation, climate and lithology of the watershed, we studied the largest, in terms of discharge, Siberian river, Yenisey, and 20 of its main tributaries, during spring flood, summer flow and winter. The working hypothesis was that the influence of bedrock composition is most pronounced in winter, when the soils are frozen and the rivers are fed by deep underground waters. Thus, we anticipated that the presence of permafrost will help to distinguish the impact of surface processes, linked to biological uptake and release, and deep soil/underground transport of Mg from mineral sources. In contrast to these expectations, no sizable differences in the Mg isotope composition of the river water (±0.1‰) for both the Yenisey tributaries and its main channel has been observed between the spring flood (May) and the winter (March) period. Those two periods are characterized by the differences of discharge and degree of lithological impact on element source in the river water. Regardless of the season, there was no straightforward control of lithology (relative abundance of carbonates, basalts, granites and sedimentary rocks) on δ26Mg in the main tributaries of the Yenisey river. Our findings suggest that the use of riverine Mg isotope signature for tracing weathering mechanisms and dominant lithological impact is not straightforward at the scale of large rivers whose watersheds present multiple lithologies, variable climatic conditions and vegetation types.

Quasi-Solid-State Dual-Ion Sodium Metal Batteries for Low-Cost Energy Storage

Summary Dual-ion sodium metal||graphite batteries are a viable technology for large-scale stationary energy storage because of their high working voltages (above 4.4 V versus Na/Na+) and the low cost of electrode materials. However, traditional liquid electrolytes generally suffer from severe decomposition at such a high voltage, which results in poor cycle life. Herein, we report a stable dual-ion sodium metal battery employing a multifunctional gel polymer electrolyte, which was facilely prepared by in situ polymerizing an ethoxylated pentaerythritol tetraacrylate monomer in an optimized liquid electrolyte with fluoroethylene carbonate as co-solvent and 1,3-propanesultone as additive. This quasi-solid-state electrolyte not only exhibits high oxidative resistance and constructs stable protective layers on the electrode surfaces but also effectively facilitates homogeneous anion and cation fluxes and suppresses the sodium dendrite growth. The as-developed quasi-solid-state dual-ion batteries delivered a high capacity with long cycle life, which could be applied for low-cost energy storage.

Near field non-invasive electrophysiology of retrotrapezoid nucleus using amperometric cation sensor

Central chemoreception is the process whereby the brainstem senses blood gas levels and adjusts homeostatic functions such as breathing and cardiovascular tone accordingly. Rodent evidence suggests that the retrotrapezoid nucleus (RTN) is a master regulator of central chemoreception, in particular, through direct sensation of acidosis induced by CO2 levels. The oscillatory dynamics caused by pH changes as sensed by the RTN surface and its relationship to the fluctuations in cation flux is not clearly understood due to the current limitations of electrophysiology tools and this article presents our investigations to address this need. A cation selective sensor fabricated from polypyrrole doped with dodecyl benzenesulfonate (PPy (DBS)) is placed over RTN in an ex-vivo en bloc brain and changes in cation concentration in the diffusion limited region above the RTN is measured due to changes in externally imposed basal pH. The novelty of this technique lies in its feasibility to detect cation fluxes from the cells in the RTN region without having to access either sides of the cell membrane. Owing to the placement of the sensor in close proximity to the tissue, we refer to this technique as near-field electrophysiology. It is observed that lowering the pH in the physiological range (7.4–7.2) results in a significant increase in cation concentration in the vicinity of RTN with a median value of ~5 μM. The utilization of such quantifiable measurement techniques to detect sub-threshold brain activity may help provide a platform for future neural network architectures. Findings from this paper present a quantifiable, sensitive, and robust electrophysiology technique with minimal damage to the underlying tissue.

Base Cation Fluxes from the Stemflow in Three Mixed Plantations in the Rainy Zone of Western China

Base cation transfer from stemflow is an important process for nutrient transfer and plays a key role in maintaining the balance of soil nutrient pools. To research the differences of stemflow chemistry in mixed plantations, we conducted a continuous field experiment in the rainy zone of Western China from December 2016 to November 2017. Three representative mixed plantations, including a conifer–broadleaved mixed plantation, a deciduous broadleaved mixed plantation and a multispecies mixed plantation, were selected to investigate the concentration and flux characteristics of K+, Na+, Ca2+ and Mg2+ in stemflow. The results showed that: (1) the K+, Na+, Ca2+ and Mg2+ fluxes ranged from 1.75 to 2.44 kg ha−1 year−1, 0.14 to 0.24 kg ha−1 year−1, 1.25 to 2.11 kg ha−1 year−1, and 0.40 to 0.60 kg ha−1 year−1 in these mixed plantations during the one-year observation, and the annual or seasonal (i.e., rainy or dry season) base cation fluxes in the stemflow varied slightly with the plantation types; (2) broadleaved trees had a higher average stemflow base cation contribution rate and flux-based enrichment ratio than coniferous trees, and the enrichment ratios showed a decreasing tendency with increasing trunk diameter; (3) the stemflow base cation concentration was higher in the dry season, while flux was observed to be higher in the rainy season. These results suggested that increasing the proportion of broadleaved species in mixed plantations might improve soil nutrient content and benefit material cycling in subtropical forest ecosystems.

Evidence for accelerated weathering and sulfate export in high alpine environments

High elevation alpine ecosystems—the ‘water towers of the world’—provide water for human populations around the globe. Active geomorphic features such as glaciers and permafrost leave alpine ecosystems susceptible to changes in climate which could also lead to changing biogeochemistry and water quality. Here, we synthesize recent changes in high-elevation stream chemistry from multiple sites that demonstrate a consistent and widespread pattern of increasing sulfate and base cation concentrations or fluxes. This trend has occurred over the past 30 years and is consistent across multiple sites in the Rocky Mountains of the United States, western Canada, the European Alps, the Icelandic Shield, and the Himalayas in Asia. To better understand these recent changes and to examine the potential causes of increased sulfur and base cation concentrations in surface waters, we present a synthesis of global records as well as a high resolution 33 year record of atmospheric deposition and river export data from a long-term ecological research site in Colorado, USA. We evaluate which factors may be driving global shifts in stream chemistry including atmospheric deposition trends and broad climatic patterns. Our analysis suggests that recent changes in climate may be stimulating changes to hydrology and/or geomorphic processes, which in turn lead to accelerated weathering of bedrock. This cascade of effects has broad implications for the chemistry and quality of important surface water resources.

Atmospheric contribution to cations cycling in highly weathered catchment, Guadeloupe (Lesser Antilles)

The important fertilizing role of atmospheric dust, and particularly African dust, in tropical rainforests is increasingly recognized but still poorly quantified. To better evaluate dust input into the Caribbean basin, we sampled critical zone compartments of a small forested volcanic catchment in Guadeloupe (soils, parent rock, atmospheric dust, plants, soil solutions, stream and rain waters). The aims of this study are to track sources of cation nutrients (Ca, Mg, K, Sr) developed on highly weathered soil in the rainforest of Guadeloupe, to quantify plant recycling of these nutrients, and to identify constraints on regolith development and its associated nutrient pool.In the Quiock Creek catchment, a large isotopic range of 87Sr/86Sr and εNd values was observed despite the small scale of observation. Sr isotopic composition of the dissolved load varied from 0.7084 in rainfall to 0.7110 in soil solution, whereas it ranges between 0.7068 and 0.7153 for soil samples and between 0.7096 and 0.7102 for plants. The Nd isotopic composition varied between -8.39 in near-surface soil samples to 2.71 in deeper soil. All samples had an intermediate signature between that of the bedrock endmember (87Sr/86Sr=0.7038; εNd=4.8) and the atmospheric endmember (sea salt: 87Sr/86Sr=0.7092 and Saharan dust: 87Sr/86Sr=0.7187, εNd=-11.5).The regolith was built on pyroclastic deposits, but, because of extreme leaching, the regolith has lost its original bedrock signature and inherited an exogenous atmospheric signature. Our results show that only the chemical weathering of the fresh near-surface minerals can provide nutrients to the ecosystem (first 30cm). However, this dust weathering is too low to sustain the tropical forest ecosystem on its own. The cationic mass balance at the catchment scale, as well as the Sr isotopic signature, show that cation and Sr fluxes are of atmospheric origin only and that original bedrock no longer participates in nutrient cycles. The vegetation reflects the 87Sr/86Sr of the dissolved pool of atmospheric Sr.At the soil-plant scale, the cation-nutrient fluxes provided by vegetation (litter fall+leaf excretion) are major compared to input and output fluxes. The annual Ca, K, Sr and Mg fluxes within the vegetation are, respectively, 31, 28, 20 and 3 times greater than the exported fluxes at the outlet of the basin. The residence time of nutrients in the vegetation is 16 years for K and close to 45 years for Sr, Ca and Mg. These results emphasize the highly efficient vegetative turnover that dominates the nutrient cycle in the Quiock Creek catchment.This first characterization of biogeochemical cycles in the Guadeloupean rainforest suggests that the forest community of Quiock Creek is sustained by a small near-surface nutrient pool disconnected from the deep volcanic bedrock. We also demonstrated that, even with efficient nutrient recycling, Saharan dust plays a significant role in maintaining ecosystem productivity in Guadeloupe over long-time scales.

Impairment of Membrane Repolarization Accompanies Axon Transport Deficits in Glaucoma.

Glaucoma is a leading cause of blindness worldwide, resulting from degeneration of retinal ganglion cells (RGCs), which form the optic nerve. In glaucoma, axon transport deficits appear to precede structural degeneration of RGC axons. The period of time between the onset of axon transport deficits and the structural degeneration of RGC axons may represent a therapeutic window for the prevention of irreversible vision loss. However, it is unclear how deficits in axon transport relate to the electrophysiological capacity of RGCs to produce and maintain firing frequencies that encode visual stimuli. Here, we examined the electrophysiological signature of individual RGCs in glaucomatous retina with respect to axon transport facility. Utilizing the Microbead Occlusion Model of murine ocular hypertension, we performed electrophysiological recordings of RGCs with and without deficits in anterograde axon transport. We found that RGCs with deficits in axon transport have a reduced ability to maintain spiking frequency that arises from elongation of the repolarization phase of the action potential. This repolarization phenotype arises from reduced cation flux and K+ dyshomeostasis that accompanies pressure-induced decreases in Na/K-ATPase expression and activity. In vitro studies with purified RGCs indicate that elevated pressure induces early internalization of Na/K-ATPase that, when reversed, stabilizes cation flux and prevents K+ dyshomeostasis. Furthermore, pharmacological inhibition of the Na/K-ATPase is sufficient to replicate pressure-induced cation influx and repolarization phase phenotypes in healthy RGCs. These studies suggest that deficits in axon transport also likely reflect impaired electrophysiological function of RGCs. Our findings further identify a failure to maintain electrochemical gradients and cation dyshomeostasis as an early phenotype of glaucomatous pathology in RGCs that may have significant bearing on efforts to restore RGC health in diseased retina.

Novel electrodialysis membranes with hydrophobic alkyl spacers and zwitterion structure enable high monovalent/divalent cation selectivity

Development of monovalent cations perm-selective membranes (MCPMs) for electrodialysis with the ability to improve cation flux, selectivity and reduce membrane swelling are the major concerns in different industrial applications, such as seawater desalination and wastewater purification. We designed and fabricated the novel MCPMs of quaternized poly(2,6-dimethyl phenylene oxide)s containing different lengths of alkyl spacers which were grafted directly to the nitrogen-centered cations connected to hydrophilic carboxylic and sulfonic acids groups. Pendant chains were in charge of tuning the membrane hydrophobicity and promoting the microphase separation. We observed that during changing the hydrophobicity of MCPMs, higher cation flux, greater perm-selectivity and more dimensional stability of monovalent cations perm-selective membrane can be achieved. The cations selectivity of prepared MCPMs was measured from electrodialysis in a Na+/Mg2+ system and compared with the commercial monovalent cation selective NeoseptaTM CIMS membrane. Highest perm-selectivity (PMg+2Na+) that reached up to 25.26 was observed for the MCPMs with the longest hydrophobic pendant chain which demonstrated that enhancement of membranes hydrophobicity considerably improved the monovalent cation perm-selectivity. These observations are quite interesting to expedite the improvement of monovalent cations perm-selective membranes for electrodialysis.

Sensitization of avian pathogenic Escherichia coli to amoxicillin in vitro and in vivo in the presence of surfactin.

The purpose of this study is to assess the antibiotics adjuvant effect of surfactin for boosting the treatment effect of amoxicillin. Surfactin is used as a surfactant to mediate flux of mono-and divalent cations, such as calcium, across lipid bilayer membranes. In this study, we demonstrated that surfactin can increase the activity of amoxicillin against avian pathogenic Escherichia coli (APEC) in vitro with antimicrobial assays such as minimum inhibitory concentrations (MIC) and fractional inhibitory concentration (FIC). Additionally in the model of chick infection, surfactin exerted adjuvant effects with amoxicillin against APEC by lowering the numerical value of mortality and liver bacterial loads, and regulating the expression of inflammatory cytokines et al. We concluded that surfactin can act as a novel antimicrobial adjuvant with amoxicillin against AEPC infection in chicken.

Inflammasome inhibition blocks cardiac glycoside cell toxicity

Chronic heart failure and cardiac arrhythmias have high morbidity and mortality, and drugs for the prevention and management of these diseases are a large part of the pharmaceutical market. Among these drugs are plant-derived cardiac glycosides, which have been used by various cultures over millennia as both medicines and poisons. We report that digoxin and related compounds activate the NLRP3 inflammasome in macrophages and cardiomyocytes at concentrations achievable during clinical use. Inflammasome activation initiates the maturation and release of the inflammatory cytokine IL-1β and the programmed cell death pathway pyroptosis in a caspase-1–dependent manner. Notably, the same fluxes of potassium and calcium cations that affect heart contraction also induce inflammasome activation in human but not murine cells. Pharmaceuticals that antagonize these fluxes, including glyburide and verapamil, also inhibit inflammasome activation by cardiac glycosides. Cardiac glycoside–induced cellular cytotoxicity and IL-1β signaling are likewise antagonized by inhibitors of the NLRP3 inflammasome or the IL-1 receptor–targeting biological agent anakinra. Our results inform on the molecular mechanism by which the inflammasome integrates the diverse signals that activate it through secondary signals like cation flux. Furthermore, this mechanism suggests a contribution of the inflammasome to the toxicity and adverse events associated with cardiac glycosides use in humans and that targeted anti-inflammatories could provide an additional adjunct therapeutic countermeasure.

Ca2+ flux through splice variants of the ATP-gated ionotropic receptor P2X7 is regulated by its cytoplasmic N terminus

Activation of ionotropic P2X receptors increases free intracellular Ca2+ ([Ca2+] i ) by initiating a transmembrane cation flux. We studied the "a" and "k" splice variants of the rat purinergic P2X7 receptor (rP2X7aR and rP2X7kR) to exhibit a significant difference in Ca2+ flux through this channel. This difference is surprising because the variants share absolute sequence identity in the area of the pore that defines ionic selectivity. Here, we used patch-clamp fluorometry and chimeric receptors to show that the fraction of the total current carried by Ca2+ is a function of the primary sequence of the cytoplasmic N terminus. Using scanning mutagenesis, we identified five sites within the N terminus that respond to mutagenesis with a decrease in fractional calcium current and an increase in permeability to the polyatomic cation, N-methyl-d-glucamine (NMDG+), relative to Na+ (PNMDG/PNa). We tested the hypothesis that these sites line the permeation pathway by measuring the ability of thiol-reactive MTSET+ to alter the current of cysteine-substituted variants, but we detected no effect. Finally, we studied the homologous sites of the rat P2X2 receptor (rP2X2R) and observed that substitutions at Glu17 significantly reduced the fractional calcium current. Taken together, our results suggest that a change in the structure of the N terminus alters the ability of an intra-pore Ca2+ selectivity filter to discriminate among permeating cations. These results are noteworthy for two reasons: they identify a previously unknown outcome of mutagenesis of the N-terminal domain, and they suggest caution when assigning structure to function for truncated P2X receptors that lack a part of the N terminus.

Zwitterion structure membrane provides high monovalent/divalent cation electrodialysis selectivity: Investigating the effect of functional groups and operating parameters

Monovalent cation perm-selective membranes (MCPMs) with enhanced monovalent flux and the capability to reject multivalent cations are critical; however, their realization remains challenging in various industrial applications, such as seawater desalination and wastewater purification. To achieve this criterion, we designed and synthesized a series of MCPMs with a zwitterion structure comprising three quaternary ammonium groups, two carboxylic acids, and one sulfonic acid group. These functional groups act to balance the cation flux and perm-selectivity of the MCPM. The cation fluxes and perm-selectivity of the fabricated MCPMs were investigated for Na+/Mg2+ and Li+/Mg2+ systems. High perm-selectivities of 58.4 and 16.5 were obtained for (PMg2+Na+) and (PMg2+Li+) systems, respectively, using a QPO/DAN-SA-5 membrane. The performance of the MCPMs was compared with the state-of-art commercial monovalent cation selective membrane NeoseptaTM CIMS. The influence of feed concentration and current density on the cation fluxes and perm-selectivity was examined, and the pH was measured to investigate the effect of concentration polarization and water splitting on electrodialysis. Moreover, the presence of various functional groups in the membrane matrix provided additional insights into electrostatic repulsive and interaction effects. The zwitterion structure of the MCPM was capable of tuning the cation flux and perm-selectivity. Our study provides an effective strategy for developing MCPMs with high cation flux and ion perm-selectivity.

The S. cerevisiae cation translocation protein Trk1 is functional without its “long hydrophilic loop” but LHL regulates cation translocation activity and selectivity

In Saccharomyces cerevisiae, K+-uptake under K+-limiting conditions is largely mediated by the cation translocation systems Trk1 and Trk2 belonging to the family of SKT proteins. They are related to two-transmembrane-domain (inward rectifying K-) channels but unlike the symmetrical tetrameric structure of K-channels, a single Trk contains four pore-forming domains (A-D) encoded on one polypeptide chain. Between domains A and B Trks contain large cytosolic regions dubbed “long hydrophilic loop” (LHL). LHLs are not homologous/similar to any other identified protein (domain) and also show little similarity between Trk1 and Trk2. Here we demonstrate that Trk1 is functional without LHL. However, in growth experiments NaCl sensitivity of Trk1[ΔLHL] expressing cells is increased under K+-limiting conditions compared to full-length Trk1. Non-invasive ion flux measurements showed that K+-influx through Trk1 and Trk1[ΔLHL] is decreased in the presence of surplus Na+ due to permeability of the proteins for both cations and competition between them. Trk1[ΔLHL] is less affected than full-length Trk1 because it is more selective for K+ over Na+. Furthermore, K+ re-uptake after starvation is delayed and decreased in Trk1[ΔLHL]. Thus, a role of LHL is regulating cation fluxes through Trk1 by (i) allowing also Na+ to pass if monovalent cations (mainly K+) are limiting and (ii) by accelerating/enhancing a switch from low to high affinity ion translocation. We propose that LHL could modulate Trk1 transport properties via direct influence on a transmembrane helix (M2A) which can switch between bent and straight conformation, thereby directly modifying the radius of the pore and selectivity filter.

TRP Channels Mediated Pathological Ca2+-Handling and Spontaneous Ectopy.

Ion channel biology offers great opportunity in identifying and learning about cardiac pathophysiology mechanisms. The discovery of transient receptor potential (TRP) channels is an add-on to the opportunity. Interacting with numerous signaling pathways, being activated multimodally, and having prescribed signatures underlining acute hemodynamic control and cardiac remodeling, TRP channels regulate cardiac pathophysiology. Impaired Ca2+-handling cause contractile abnormality. Modulation of intracellular Ca2+ concentration ([Ca2+]i) is a major part of Ca2+-handling processes in cardiac pathophysiology. TRP channels including TRPM4 regulate [Ca2+]i, Ca2+-handling and cardiac contractility. The channels modulate flux of divalent cations, such as Ca2+ during Ca2+-handling and cardiac contractility. Seminal works implicate TRPM4 and TRPC families in intracellular Ca2+ homeostasis. Defective Ca2+-homeostasis through TRP channels interaction with Ca2+-dependent regulatory proteins such as sodium calcium exchanger (NCX) results in abnormal Ca2+ handling, contractile dysfunction and in spontaneous ectopy. This review provides insight into TRP channels mediated pathological Ca2+-handling and spontaneous ectopy.

Pressure-dependent modulation of inward-rectifying K+ channels: implications for cation homeostasis and K+ dynamics in glaucoma

Glaucoma is the leading cause of blindness worldwide, resulting from degeneration of retinal ganglion cells (RGCs), which form the optic nerve. Prior to structural degeneration, RGCs exhibit physiological deficits. Müller glia provide homeostatic regulation of ions that supports RGC physiology through a process called K+ siphoning. Recent studies suggest that several retinal conditions, including glaucoma, involve changes in the expression of K+ channels in Müller glia. To clarify whether glaucoma-related stressors directly alter expression and function of K+ channels in Müller glia, we examined changes in the expression of inwardly rectifying K+ (Kir) channels and two-pore domain (K2P) channels in response to elevated intraocular pressure (IOP) in vivo and in vitro in primary cultures of Müller glia exposed to elevated hydrostatic pressure. We then measured outcomes of cell health, cation homeostasis, and cation flux in Müller glia cultures. Transcriptome analysis in a murine model of microbead-induced glaucoma revealed pressure-dependent downregulation of Kir and K2P channels in vivo. Changes in the expression and localization of Kir and K2P channels in response to elevated pressure were also found in Müller glia in vitro. Finally, we found that elevated pressure compromises the plasma membrane of Müller glia and induces cation dyshomeostasis that involves changes in ion flux through cation channels. Pressure-induced changes in cation flux precede both cation dyshomeostasis and membrane compromise. Our findings have implications for Müller glia responses to pressure-related conditions, i.e., glaucoma, and identify cation dyshomeostasis as a potential contributor to electrophysiological impairment observed in RGCs of glaucomatous retina.