Membrane Channels Research Articles

Aquaporins in Biliary Function: Pathophysiological Implications and Therapeutic Targeting

Aquaporins (AQPs) are transmembrane proteins permeable to water and a series of small solutes. AQPs play a key role in pathways of hepatobiliary secretion at the level of the liver, bile ducts, and gallbladder. AQP8 and -9 are pivotal in facilitating the osmotic water movement of hepatic bile, which is composed of 95% water. In the biliary tract, AQP1 and -4 are involved in the rearrangement of bile composition by mechanisms of reabsorption/secretion of water. In the gallbladder, AQP1 and -8 are also involved in trans-epithelial bidirectional water flow with the ultimate goal of bile concentration. Pathophysiologically, AQPs have been indicated as players in several hepatobiliary disorders, including cholestatic diseases and cholesterol cholelithiasis. Research on AQP function and the modulation of AQP expression is in progress, with the identification of potent and homolog-specific compounds modulating the expression or inhibiting these membrane channels with promising pharmacological developments. This review summarizes the contribution of AQPs in physiological and pathophysiological stages related to hepatobiliary function.

A two-faced membrane channel.

Contrasting surface properties activate a feedback loop system for a complete oil-and-water separation.

Action potential threshold variability for different electrostimulation models and its potential impact on occupational exposure limit values.

Occupational exposure limit values (ELVs) for body internal electric fields can be derived from thresholds for action potential generation. These thresholds can be calculated with electrostimulation models. The spatially extended nonlinear node model (SENN) is often used to determine such thresholds. Important parameters of these models are the membrane channel dynamics describing the ionic transmembrane currents as well as the temperature at which the models operate. This work compares action potential thresholds for five different membrane channel dynamics used with the SENN model. Furthermore, two more detailed double-cable models by Gaines et al. (MRG-Sensory and MRG-Motor) are also considered in this work. Thresholds calculated with the SENN model and the MRG models are compared for frequencies between 1 Hz and 100 kHz and temperatures at 22°C and 37°C. Results show that MRG thresholds are lower than SENN thresholds. Deriving alternative ELVs from these thresholds shows that the alternative ELVs can change significantly with different ion channel dynamics (up to a factor of 22). Using the double cable model could lead to approximately ten times lower alternative exposure limit values. On the contrary, using the SENN model with different membrane channel dynamics could also lead to higher alternative exposure limit values. Therefore, future exposure guidelines should take the influence of different electrostimulation models into account when deriving ELVs.

FREE FATTY ACIDS INHIBIT AN ION-COUPLED MEMBRANE TRANSPORTER BY DISSIPATING THE ION GRADIENT

Glutamate is the main excitatory transmitter in the mammalian central nervous system; glutamate transporters keep the synaptic glutamate concentrations at bay for normal brain function. Arachidonic acid (AA), docosahexaenoic acid (DHA), and other unsaturated fatty acids modulate glutamate transporters in cell- and tissue slices-based studies. Here, we investigated their effect and mechanism using a purified archaeal glutamate transporter homolog reconstituted into the lipid membranes. AA, DHA, and related fatty acids irreversibly inhibited the sodium-dependent concentrative substrate uptake into lipid vesicles within the physiologically relevant concentration range. In contrast, AA did not inhibit amino acid exchange across the membrane. The length and unsaturation of the aliphatic tail affect inhibition, and the free carboxylic headgroup is necessary. The inhibition potency did not correlate with the fatty acid effects on the bilayer deformation energies. AA does not affect the conformational dynamics of the protein, suggesting it does not inhibit structural transitions necessary for transport. Single-transporter and membrane voltage assays showed that AA and related fatty acids mediate cation leak, dissipating the driving sodium gradient. Thus, such fatty acids can act as cation ionophores, suggesting a general modulatory mechanism of membrane channels and ion-coupled transporters.

Distinct Strategies Regulate Correlated Ion Channel mRNAs and Ionic Currents in Continually versus Episodically Active Neurons.

Relationships among membrane currents allow central pattern generator (CPG) neurons to reliably drive motor programs. We hypothesize that continually active CPG neurons utilize activity-dependent feedback to correlate expression of ion channel genes to balance essential membrane currents. However, episodically activated neurons experience absences of activity-dependent feedback and, thus, presumably employ other strategies to coregulate the balance of ionic currents necessary to generate appropriate output after periods of quiescence. To investigate this, we compared continually active pyloric dilator (PD) neurons with episodically active lateral gastric (LG) CPG neurons of the stomatogastric ganglion (STG) in male Cancer borealis crabs. After experimentally activating LG for 8 h, we measured three potassium currents and abundances of their corresponding channel mRNAs. We found that ionic current relationships were correlated in LG's silent state, but ion channel mRNA relationships were correlated in the active state. In continuously active PD neurons, ion channel mRNAs and ionic currents are simultaneously correlated. Therefore, two distinct relationships exist between channel mRNA abundance and the ionic current encoded in these cells: in PD, a direct correlation exists between Shal channel mRNA levels and the A-type potassium current it carries. Conversely, such channel mRNA-current relationships are not detected and appear to be temporally uncoupled in LG neurons. Our results suggest that ongoing feedback maintains membrane current and channel mRNA relationships in continually active PD neurons, while in LG neurons, episodic activity serves to establish channel mRNA relationships necessary to produce the ionic current profile necessary for the next bout of activity.

PilY1 regulates the dynamic architecture of the type IV pilus machine in Pseudomonas aeruginosa

Type IV pili (T4P) produced by the pathogen Pseudomonas aeruginosa play a pivotal role in adhesion, surface motility, biofilm formation, and infection in humans. Despite the significance of T4P as a potential therapeutic target, key details of their dynamic assembly and underlying molecular mechanisms of pilus extension and retraction remain elusive, primarily due to challenges in isolating intact T4P machines from the bacterial cell envelope. Here, we combine cryo-electron tomography with subtomogram averaging and integrative modelling to resolve in-situ architectural details of the dynamic T4P machine in P. aeruginosa cells. The T4P machine forms 7-fold symmetric cage-like structures anchored in the cell envelope, providing a molecular framework for the rapid exchange of major pilin subunits during pilus extension and retraction. Our data suggest that the T4P adhesin PilY1 forms a champagne-cork-shaped structure, effectively blocking the secretin channel in the outer membrane whereas the minor-pilin complex in the periplasm appears to contact PilY1 via the central pore of the secretin gate. These findings point to a hypothetical model where the interplay between the secretin protein PilQ and the PilY1-minor-pilin priming complex is important for optimizing conformations of the T4P machine in P. aeruginosa, suggesting a gate-keeping mechanism that regulates pilus dynamics.

TRPV4-A Multifunctional Cellular Sensor Protein with Therapeutic Potential.

Transient receptor potential vanilloid (TRPV) channel proteins belong to the superfamily of TRP proteins that form cationic channels in the animal cell membranes. These proteins have various subtype-specific functions, serving, for example, as sensors for pain, pressure, pH, and mechanical extracellular stimuli. The sensing of extracellular cues by TRPV4 triggers Ca2+-influx through the channel, subsequently coordinating numerous intracellular signaling cascades in a spatio-temporal manner. As TRPV channels play such a wide role in various cellular and physiological functions, loss or impaired TRPV protein activity naturally contributes to many pathophysiological processes. This review concentrates on the known functions of TRPV4 sensor proteins and their potential as a therapeutic target.

Effects of droplet dynamical behavior in flow channel of proton exchange membrane fuel cell under vibration conditions on cell performance

Proton exchange membrane fuel cells are subjected to severe vibration in aerospace applications. Understanding the droplet transport characteristics in the flow channelunder vibration conditions is essential for improving cell performance. However, the underlying patterns and mechanisms of the vibration effects on cell performance and its internal water transport remain unclear, and there is a lack of improvement methods for drainage under vibration conditions. This study experimentally investigates the effect of vibration on cell performance. Experimental results indicate that vibration predominantly affects cell performance through its modulation of water transport. Therefore, the droplet dynamic behavior in the flow channel is further studied using the volume of fluid method. The results indicate that vibrations can enhance the average performance of the fuel cells, with the largest increase of 8.30 %. This is attributed to vibrations promoting the detachment of droplets from the gas diffusion layer surface and reducing the water coverage ratio on said surface. Under conditions of low gas velocity, high surface hydrophobicity, and large droplet size, droplets exhibited oscillatory and jumping behavior in the flow channel due to vibration, resulting in the largest 53.5 % increase in peak water coverage ratio on the gas diffusion layer surface compared to no-vibration conditions. Furthermore, enhancing the hydrophobicity of the gas diffusion layer and the hydrophilicity of the channel walls promotes droplet detachment and discharge compared to no-vibration, as well as contributing to the improvement of vibration effects on the drainage process.

Vitamin D in cardiac fibroblasts: new evidence for a TRP-mediated non-genomic pathway

Abstract Background/Introduction Vitamin D’s (VD) role transcends phosphocalcic metabolism to affect different systems, notably the cardiovascular system in health and diseases. Beyond its genomic effect, VD act through non-genomic calcium (Ca2+) signaling pathways, hinting at a broader spectrum of physiological impacts. Despite the established interactions with cardiomyocytes via the Vitamin D Receptor (VDR), little is known about VD and cardiac fibroblast, a pivotal cell player in cardiac function and disease. Purpose This research aims to reveal Vitamin D's role in modulating cardiac fibroblast function through Transient Receptor Potential (TRP) channels. Methods Utilizing primary cardiac fibroblasts from human and rats, our investigation focused on intracellular calcium signaling. Through Ca2+ imaging techniques combined to synthetic fluorescent VD analogue, we explored Vitamin D's behavior within the cell. The study further employed biochemical assays to elucidate the interaction between VDR on the cell membrane and TRP channels signaling, providing a detailed map of the cellular choreography orchestrated by VD within cardiac fibroblasts. In addition, in vitro and ex vivo heart perfusion experiments were incorporated to assess cardiac cGMP production in response to VD. Results Our findings reveal a unique pathway wherein VD induces Ca2+ oscillations in human and rat cardiac fibroblasts specifically through the TRPC3 channel, sidelining other calcium sources. This process is regulated by the interaction between TRPC3 and the membrane-bound VDR, harmonizing with phospholipase C signaling to a crescendo of cGMP production in cardiac fibroblasts, and across the entire heart. This was associated with less pro-fibrotic potential of cardiac fibroblasts. Conclusion This study provides the first evidence of a TRP-mediated, VD non-genomic pathway within human and rat cardiac fibroblasts. Our findings herald a promising horizon for investigating vitamin D’s antifibrotic potential in heart disease.

Spatial Size Manipulation of 1D/2D Channels in Covalent Organic Framework Membranes Through Dopamine Chemistry for Ion Separations

AbstractCovalent organic framework (COF) membranes feature with well‐developed 1D in‐plane pores and parallelly arranged 2D interlayer gallery, presenting promising platform for precise separations. However, it remains a formidable challenge to construct and regulate membrane channels at angstrom scale. Herein, pH‐sensitive dopamine is taken advantage to elaborately engineer the spatial size of 1D/2D channels in COF membranes for the separations of alkali metal ions. Acid treatment allows monomolecular dopamine to segment 1D in‐plane pores of COF membrane, achieving ultramicroporous regulation from 1.25 nm to 0.71 nm, which enables high selectivity of 18.7 for K+/Li+ separation. Molecular dynamics simulations reveal the higher dehydration degree, weaker channel‐cation interaction and faster diffusion coefficient of K+ than Li+. For alkaline treatment, dopamine self‐polymerizes to form nanoparticles between COF layers, which enlarges the 2D interlayer channels from 0.33 nm to 0.45 nm in COF membrane, enabling high‐permeance ion/molecule separations. The water permeance increases 86.7% to 404 L m−2 h−1 bar−1, without the sacrifice of membrane sieving ability. Both cation separation and ion/molecule separation performances outperform the current state‐of‐the‐art membranes. This dopamine‐mediated channel engineering strategy may provide the new insights for the design of membrane channels in precise separations.

Generation and Characterization of Three Novel Mouse Mutant Strains Susceptible to Audiogenic Seizures.

The mechanisms of epileptogenesis after brain injury, ischemic stroke, or brain tumors have been extensively studied. As a result, many effective antiseizure drugs have been developed. However, there are still many patients who are resistant to therapy. The molecular and genetic bases regarding such drug-resistant seizures have been poorly elucidated. In many cases, heavy seizures are instigated by brain development malformations and often caused by gene mutations. Such malformations can be demonstrated in mouse models by generating mutant strains. One of the most potent mutagens is ENU (N-ethyl-N-nitrosourea). In the present study, we describe three novel mutant strains generated by ENU-directed mutagenesis. Two of these strains present a very strong epileptic phenotype triggered by audiogenic stimuli (G9-1 and S5-1 strains). The third mouse strain is characterized by behavioral disorders and hyperexcitation of neuronal networks. We identified changes in the expression of those genes encoding neurotransmission proteins in the cerebral cortexes of these mice. It turned out that the G9-1 strain demonstrated the strongest disruptions in the expression of those genes encoding plasma membrane channels, excitatory glutamate receptors, and protein kinases. On the other hand, the number of GABAergic neurons was also affected by the mutation. All three lines are characterized by increased anxiety, excitability, and suppressed motor and orientational-exploratory activities. On the other hand, the strains with an epileptic phenotype-G9-1 and S5-1ave reduced learning ability, and the A9-2 mice line retains high learning ability.

Transcriptome analysis of tilapia streptococcus agalactiae in response to baicalin.

Streptococcus agalactiae (S. agalactiae) is a highly pathogenic bacterial pathogen in aquatic animals. Our previous study has demonstrated the significant inhibitory effect of baicalin on β-hemolytic/cytolytic activity, which is a key virulence factor of S. agalactiae. In this study, we aimed to elucidate the mechanism underlying baicalin's inhibition of S. agalactiae β-hemolytic/cytolytic activity by transcriptomic analysis. Bacteria were exposed to 39.06µg/mL baicalin for 6h, and their β-hemolytic/cytolytic activities were assessed using blood plates. Then, the differentially expressed genes (DEGs) were identified and characterized by RNA sequencing (RNA-Seq), and further confirmed using the qRT-PCR. A total of 10 DEGs with 7 significantly up-regulated and 3 significantly down-regulated, were found to be affected significantly under baicalin treatment. These DEGs were associated with 5 biological processes, 5 cellular components, and 3 molecular functions. They were primarily enriched in 3 pathways: lacD and lacC in galactose metabolism, lrgA and lrgB in the two-component system, and ribH/rib4 in riboflavin metabolism. These suggested that baicalin might inhibit the conversion of pyruvate to acetyl-CoA and malonyl-CoA, which are crucial precursors for β-hemolysin/cytolysin synthesis, and result in the accumulation of pyruvate, suppress the expressions of pyruvate cell membrane channel protein genes lrgA and lrgB. Baicalin could compensatory up-regulate the expressions of tryptophan/tyrosine ABC transporter family genes, ABC.X4.A, ABC.X4.P, and ABC.X4.S by inhibiting the expression of cyl A/B in cyl operons. Moreover, it hinders the conversion of D-glucose 1-phosphate to the dTDP-L-rhamnose pathway and leads to a deficiency of L-rhamnose, an important precursor for β-hemolysin/cytolysin synthesis.

Genome-Wide Identification of the Cyclic Nucleotide-Gated Ion Channel Gene Family and Expression Profiles Under Low-Temperature Stress in Luffa cylindrica L.

Cyclic nucleotide-gated ion channels (CNGCs) are cell membrane channel proteins for calcium ions. They have been reported to play important roles in survival and in the responses to environmental factors in various plants. However, little is known about the CNGC family and its functions in luffa (Luffa cylindrica L.). In this study, a bioinformatics-based method was used to identify members of the CNGC gene family in L. cylindrica. In total, 20 LcCNGCs were detected, and they were grouped into five subfamilies (I, II, Ⅲ, IV-a, and IV-b) in a phylogenetic analysis with CNGCs from Arabidopsis thaliana (20 AtCNGCs) and Momordica charantia (17 McCNGCs). The 20 LcCNGC genes were unevenly distributed on 11 of the 13 chromosomes in luffa, with none on Chromosomes 1 and 5. The members of each subfamily encoded proteins with highly conserved functional domains. An evolutionary analysis of CNGCs in luffa revealed three gene losses and a motif deletion. An examination of gene replication events during evolution indicated that two tandemly duplicated gene pairs were the primary driving force behind the evolution of the LcCNGC gene family. PlantCARE analyses of the LcCNGC promoter regions revealed various cis-regulatory elements, including those responsive to plant hormones (abscisic acid, methyl jasmonate, and salicylic acid) and abiotic stresses (light, drought, and low temperature). The presence of these cis-acting elements suggested that the encoded CNGC proteins may be involved in stress responses, as well as growth and development. Transcriptome sequencing (RNA-seq) analyses revealed tissue-specific expression patterns of LcCNGCs in various plant parts (roots, stems, leaves, flowers, and fruit) and the upregulation of some LcCNGCs under low-temperature stress. To confirm the accuracy of the RNA-seq data, 10 cold-responsive LcCNGC genes were selected for verification by quantitative real-time polymerase chain reaction (RT-qPCR) analysis. Under cold conditions, LcCNGC4 was highly upregulated (>50-fold increase in its transcript levels), and LcCNGC3, LcCNGC6, and LcCNGC13 were upregulated approximately 10-fold. Our findings provide new information about the evolution of the CNGC family in L. cylindrica and provide insights into the functions of the encoded CNGC proteins.

Molecular permeation through large pore channels: computational approaches and insights.

Computational methods such as molecular dynamics (MD) have illuminated how single-atom ions permeate membrane channels and how selectivity among them is achieved. Much less is understood about molecular permeation through eukaryotic channels that mediate the flux of small molecules (e.g. connexins, pannexins, LRRC8s, CALHMs). Here we describe computational methods that have been profitably employed to explore the movements of molecules through wide pores, revealing mechanistic insights, guiding experiments, and suggesting testable hypotheses. This review illustrates MD techniques such as voltage-driven flux, potential of mean force, and mean first-passage-time calculations, as applied to molecular permeation through wide pores. These techniques have enabled detailed and quantitative modeling of molecular interactions and movement of permeants at the atomic level. We highlight novel contributors to the transit of molecules through these wide pathways. In particular, the flexibility and anisotropic nature of permeant molecules, coupled with the dynamics of pore-lining residues, lead to bespoke permeation dynamics. As more eukaryotic large-pore channel structures and functional data become available, these insights and approaches will be important for understanding the physical principles underlying molecular permeation and as guides for experimental design.

Constructing multi-path channels in graphene oxide-based membrane for high-efficiency oil/water separation

Graphene oxide (GO) membranes have demonstrated significant potential for effective wastewater treatment; however, their tortuous and irregular water transport pathways through stacked nanosheets pose considerable challenges. In this study, we present a novel approach for fabricating faveolate-structured graphene oxide nanomesh (GONM) membranes, enhanced by the in situ growth of Co(OH)2 nanosheets to facilitate oil–water separation. The incorporation of in-plane pathways through the porous GONM, alongside the enlargement of interlayer pathways from Co(OH)2 growth, significantly improves water permeance. The nanopores present in the holey GONM reduce diffusion pathways, while intercalation of Co(OH)2 nanosheets increases channel sizes and stabilizes the GONM structure. By manipulating the mass ratio between GONM and cobalt salt, we optimized the membrane, achieving an exceptional water permeance of 224.2 L m-2h−1 bar−1, surpassing GO membranes. Additionally, the resultant membranes exhibit remarkable underwater anti-oil adhesion performance and efficient separation capabilities for a wide variety of oil-in-water emulsions, with separation efficiencies exceeding 99.1 %. This work provides valuable insights into the intentional manipulation of surface topography and hierarchical nanochannels in membrane materials, paving the way for high-efficiency water treatment solutions.

Identification of an ionic mechanism for ERα-mediated rapid excitation in neurons.

The major female ovarian hormone, 17β-estradiol (E2), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E2, but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E2-induced rapid excitations in multiple brain ERα populations. Further, genetic disruption of Clic1 in hypothalamic ERα neurons blunts the regulations of E2 on female body weight balance. In conclusion, we identified the Clic1 chloride channel as a key mediator for E2-induced rapid neuronal excitation, which may have a broad impact on multiple neurobiological processes regulated by E2.

Structural basis of α-latrotoxin transition to a cation-selective pore

The potent neurotoxic venom of the black widow spider contains a cocktail of seven phylum-specific latrotoxins (LTXs), but only one, α-LTX, targets vertebrates. This 130 kDa toxin binds to receptors at presynaptic nerve terminals and triggers a massive release of neurotransmitters. It is widely accepted that LTXs tetramerize and insert into the presynaptic membrane, thereby forming Ca2+-conductive pores, but the underlying mechanism remains poorly understood. LTXs are homologous and consist of an N-terminal region with three distinct domains, along with a C-terminal domain containing up to 22 consecutive ankyrin repeats. Here we report cryoEM structures of the vertebrate-specific α-LTX tetramer in its prepore and pore state. Our structures, in combination with AlphaFold2-based structural modeling and molecular dynamics simulations, reveal dramatic conformational changes in the N-terminal region of the complex. Four distinct helical bundles rearrange and together form a highly stable, 15 nm long, cation-impermeable coiled-coil stalk. This stalk, in turn, positions an N-terminal pair of helices within the membrane, thereby enabling the assembly of a cation-permeable channel. Taken together, these data give insight into a unique mechanism for membrane insertion and channel formation, characteristic of the LTX family, and provide the necessary framework for advancing novel therapeutics and biotechnological applications.

Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins.

Store-operated Ca2+ entry is a mechanism controlled by the filling state of the intracellular Ca2+ stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role. Two forms of Orai1, Orai1α and Orai1β, have been identified, which arises the question whether they are equally regulated by STIM proteins. We demonstrate that STIM1 preferentially activates Orai1α over STIM2, yet both STIM proteins similarly activate Orai1β. Under resting conditions, there is a pronounced association between STIM2 and Orai1α. STIM1 and STIM2 are also shown to influence the protein levels of the Orai1 variants, independently of Ca2+ influx, via lysosomal degradation. Interestingly, Orai1α and Orai1β appear to selectively regulate the protein level of STIM1, but not STIM2. These observations offer crucial insights into the regulatory dynamics between STIM proteins and Orai1 variants, enhancing our understanding of the intricate processes that fine-tune intracellular Ca2+ signaling.

Utilization of substrate specific membrane channels in liposome based biosensors: A nitrite biosensor with NirC nitrite channels

A liposome-based nitrite biosensor was prepared by encapsulating the nitrite reductase NirB enzyme and embedding the nitrite-specific NirC channels in the liposome structure. The proteoliposomes were coated on the glassy carbon electrode modified with the multi-walled carbon nanotube/chitosan matrix. The absence of channels in the liposome structure inhibits the generation of typical reduction peaks upon the addition of nitrite suggesting that ion channels are necessary for the passage of charged ions into the liposome. The response of the NirB and NirC incorporated liposome-based biosensor (CBLip/MWCNTs/CHIT/GC electrode) to the nitrite is shown to be fast and reproducible. The electrode shows a linear response between 1–500 µM nitrite concentrations. The sensitivity of the CBLip/MWCNTs/CHIT/GC electrode was 707 mA.M−1.cm−2, lower than that of the unentrapped NirB-loaded electrode (1131 mA.M−1.cm−2). While the electrode prepared with the unentrapped enzyme lost its activity in 30 days,entrapment of the enzyme in the liposome preserved the electrode activity by 55 %. The electrodes showed unexpected oxidation responses against high concentrations of sulfate and formate, theincorporation of NirC channels contributed to increasing the specificity of the electrode towards nitrite in the presence of these ions. The use of substrate-specific membrane channels in liposome-based biosensors was achieved for the first time in the present study.

Tartaric acid anion intercalated layered double hydroxides constructed a CO2-favorable transport channel in PIM-1 mixed matrix membranes for CO2/N2 separation

As a unique polymer of intrinsic microporosity, PIM-1 has great potential in mixed matrix membranes (MMMs) for gas separation with ultra-high permeability. However, the separation performance, e.g. CO2/N2 separation, is still limited by its poor selectivity. In this work, PIM-1-based MMMs containing tartaric acid anion intercalated layered double hydroxides (TA-LDH) nanofillers are successfully prepared. The uniformly dispersed TA-LDH in the PIM-1 matrix contributes to optimizing the stacking of polymer chains for accessible pores, which is conducive to CO2 diffusion. In addition, the assistant experiment and theoretical calculation point out that the -COO-, –OH between the TA-LDH layers had an affinity for CO2, creating a two-dimensional fast transport channel between the enlarged interlayer space. Compared with the pristine PIM-1 membrane, the CO2 permeability and CO2/N2 selectivity of 0.7 % TA-LDH/PIM-1 membrane is increased by 43.19 % and 105.48 %. The excellent gas separation performance with CO2 permeability of 8343.18 Barrer and CO2/N2 selectivity of 39.02 exceeds the 2019 Robson upper limit. This paves a new way to improve the gas separation performance of PIM-1-based MMMs and suggests high perspectives for real applications.