Search Results (3,303)

It has long been accepted that breathing gases that are physiologically inert include helium (He), neon (Ne), nitrogen (N₂), argon (Ar), krypton (Kr), xenon (Xe), and hydrogen (H₂). The term “inert gas” has been used to describe them due to their unusually high chemical stability. However, as investigations have advanced, many have shown that inert gas can have specific biological impacts when exposed to high pressure or atmospheric pressure. Additionally, different inert gases have different effects on intracellular signal transduction, ion channels, and cell membrane receptors, which are linked to their anesthetic and cell protection effects in normal or pathological processes. Through a selective analysis of the representative literature, this study offers a concise overview of the state of research on the biological impacts of inert gas and their molecular mechanisms. Full article

One major challenge in cellular neuroscience is to elucidate how the accurate alignment of presynaptic release sites with postsynaptic densely clustered ligand-gated ion channels at chemical synapses is achieved upon synapse assembly. The clustering of neurotransmitter receptors at postsynaptic sites is a key moment of synaptogenesis and determinant for effective synaptic transmission. The number of the ionotropic neurotransmitter receptors at these postsynaptic sites of both excitatory and inhibitory synapses is variable and is regulated by different mechanisms, thus allowing the modulation of synaptic strength, which is essential to tune neuronal network activity. Several well-regulated processes seem to be involved, including lateral diffusion within the plasma membrane and local anchoring as well as receptor endocytosis and recycling. The molecular mechanisms implicated are numerous and were reviewed recently in great detail. The role of pre-synaptically released neurotransmitters within the complex regulatory apparatus organizing the postsynaptic site underneath presynaptic terminals is not completely understood, even less for inhibitory synapses. In this mini review article, we focus on this aspect of synapse formation, summarizing and contrasting findings on the functional role of the neurotransmitters glycine and γ-aminobutyric acid (GABA) for initiation of postsynaptic receptor clustering and regulation of Cl⁻ channel receptor numbers at inhibitory synapses gathered over the last two decades. Full article

In this study, we propose a bidirectional chemical sensor platform based on a reconfigurable ion-sensitive field-effect transistor (R-ISFET) architecture. The device incorporates Ni-silicide Schottky barrier source/drain (S/D) contacts, enabling ambipolar conduction and bidirectional turn-on behavior for both p-type and n-type configurations. Channel polarity is dynamically controlled via the program gate (PG), while the control gate (CG) suppresses leakage current, enhancing operational stability and energy efficiency. A dual-control-gate (DCG) structure enhances capacitive coupling, enabling sensitivity beyond the Nernst limit without external amplification. The extended-gate (EG) architecture physically separates the transistor and sensing regions, improving durability and long-term reliability. Electrical characteristics were evaluated through transfer and output curves, and carrier transport mechanisms were analyzed using band diagrams. Sensor performance—including sensitivity, hysteresis, and drift—was assessed under various pH conditions and external noise up to 5 V_pp (i.e., peak-to-peak voltage). The n-type configuration exhibited high mobility and fast response, while the p-type configuration demonstrated excellent noise immunity and low drift. Both modes showed consistent sensitivity trends, confirming the feasibility of complementary sensing. These results indicate that the proposed R-ISFET sensor enables selective mode switching for high sensitivity and robust operation, offering strong potential for next-generation biosensing and chemical detection. Full article

Piezo1 is a mechanosensitive non-selective cation channel. Genetic alterations of the channel result in a hematologic phenotype named Hereditary Xerocytosis. With Yoda1 and, more recently, Yoda2, compounds to increase the activity of Piezo1 have become available. However, their concrete effect depends on the nano environment of the channel and hence on the cell type. Here we compare the potency of Yoda1 and Yoda2 in red blood cells (RBCs). We investigate the effect of the compounds on direct channel activity using automated patch clamp, as well as the secondary effects of channel activation on signalling molecules and cellular response. In terms of signalling, we investigate the temporal response of the second messenger Ca²⁺, and in terms of cellular response, the activity of the Gárdos channel. The opening of the Gárdos channel leads to a hyperpolarisation of the RBCs, which is measured by the Macey–Bennekou–Egée (MBE) method. Although the interpretation of the data is not straightforward, we discuss the results in a physiological context and provide recommendations for the use of Yoda1 and Yoda2 to investigate RBCs. Full article

Since the initial use of biological ion channels to detect single-stranded genomic base pair differences, label-free and highly sensitive resistive pulse sensing (RPS) with nanopores has made remarkable progress in single-molecule analysis. By monitoring transient ionic current disruptions caused by molecules translocating through a nanopore, this technology offers detailed insights into the structure, charge, and dynamics of the analytes. In this work, the RPS platforms based on biological, solid-state, and other sensing pores, detailing their latest research progress and applications, are reviewed. Their core capability is the high-precision characterization of tiny particles, ions, and nucleotides, which are widely used in biomedicine, clinical diagnosis, and environmental monitoring. However, current RPS methods involve bottlenecks, including limited sensitivity (weak signals from sub-nanometer targets with low SNR), complex sample interference (high false positives from ionic strength, etc.), and field consistency (solid-state channel drift, short-lived bio-pores failing POCT needs). To overcome this, bio-solid-state fusion channels, in-well reactors, deep learning models, and transfer learning provide various options. Evolving into an intelligent sensing ecosystem, RPS is expected to become a universal platform linking basic research, precision medicine, and on-site rapid detection. Full article

Membrane transporters play a crucial role in any cell. Identifying the substrates they translocate across membranes is important for many fields of research, such as metabolomics, pharmacology, and biotechnology. In this study, we leverage recent advances in deep learning, such as amino acid sequence embeddings with protein language models (pLMs), highly accurate 3D structure predictions with AlphaFold 2, and structure-encoding 3Di sequences from FoldSeek, for predicting substrates of membrane transporters. We test new deep learning features derived from both sequence and structure, and compare them to the previously best-performing protein encodings, which were made up of amino acid k-mer frequencies and evolutionary information from PSSMs. Furthermore, we compare the performance of these features either using a previously developed SVM model, or with a regularized feedforward neural network (FNN). When evaluating these models on sugar and amino acid carriers in A. thaliana, as well as on three types of ion channels in human, we found that both the DL-based features and the FNN model led to a better and more consistent classification performance compared to previous methods. Direct encodings of 3D structures with Foldseek, as well as structural embeddings with ProstT5, matched the performance of state-of-the-art amino acid sequence embeddings calculated with the ProtT5-XL model when used as input for the FNN classifier. Full article

The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article

Diabetic sensorimotor polyneuropathy (DSPN) is the most prevalent complication of diabetes, affecting nearly half of all persons with diabetes. It is characterized by nerve degeneration, progressive sensory loss and pain, with increased risk of ulceration and amputation. Despite its high prevalence, disease-modifying treatments for DSPN do not exist. Mitochondrial dysfunction and Ca²⁺ dyshomeostasis are key contributors to the pathophysiology of DSPN, disrupting neuronal energy homeostasis and initiating axonal degeneration. Recent findings have demonstrated that antagonism of the muscarinic acetylcholine type 1 receptor (M₁R) promotes restoration of mitochondrial function and axon repair in various neuropathies, including DSPN, chemotherapy-induced peripheral neuropathy (CIPN) and HIV-associated neuropathy. Pirenzepine, a selective M₁R antagonist with a well-established safety profile, is currently under clinical investigation for its potential to reverse neuropathy. The transient receptor potential melastatin-3 (TRPM3) channel, a Ca²⁺-permeable ion channel, has recently emerged as a downstream effector of G protein-coupled receptor (GPCR) pathways, including M₁R. TRPM3 activation enhanced mitochondrial Ca²⁺ uptake and bioenergetics, promoting axonal sprouting. This review highlights mitochondrial and Ca²⁺ signaling imbalances in DSPN and presents M₁R antagonism and TRPM3 activation as promising neuro-regenerative strategies that shift treatment from symptom control to nerve restoration in diabetic and other peripheral neuropathies. Full article

Ant venoms are rich sources of bioactive molecules, including peptide toxins with potent and selective activity on ion channels, which makes them valuable for pharmacological research and therapeutic development. Voltage-dependent potassium (Kv) channels, critical for regulating cellular excitability or cell cycle progression control, are targeted by a diverse array of venom-derived peptides. This study focuses on MYRTX_A4-Tb11a, a peptide from Tetramorium bicarinatum venom, which was previously shown to have a strong paralytic effect on dipteran species without cytotoxicity on insect cells. In the present study, we show that Tb11a exhibited no or low cytotoxicity toward mammalian cells either, even at high concentrations, while electrophysiological studies revealed a blockade of hKv1.3 activity. Additionally, Ta11a, an analog of Tb11a from the ant Tetramorium africanum, demonstrated similar Kv1.3 inhibitory properties. Structural analysis supports that the peptide acts on Kv1.3 channels through the functional dyad Y21-K25 and that the disulfide bridge is essential for biological activity, as reduction seems to disrupt the peptide conformation and impair the dyad. These findings highlight the importance of three-dimensional structure in channel modulation and establish Tb11a and Ta11a as promising Kv1.3 inhibitors. Future research should investigate their selectivity across additional ion channels and employ structure-function studies to further enhance their pharmacological potential. Full article

Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer’s disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases. Full article

Synthetic nanopores were recently demonstrated with memristive and nonlinear voltage-current behaviors, akin to ion channels in a cell membrane. Such ionic devices are considered a promising candidate for the development of brain-inspired neuromorphic computing techniques. In this work, we show the composite behavior of nanopore-array large memristors, formed with different membrane materials, pore sizes, electrolytes, and device arrangements. Anodic aluminum oxide (AAO) membranes with 5 nm and 20 nm diameter pores and track-etched polycarbonate (PCTE) membranes with 10 nm diameter pores are tested and shown to demonstrate memristive and nonlinear behaviors with approximately 10⁷–10¹⁰ pores in parallel when electrolyte concentration across the membranes is asymmetric. Ion diffusion through the large number of channels induces time-dependent electrolyte asymmetry that drives the system through different memristive states. The behaviors of series composite memristors with different configurations are also presented. In addition to helping understand fluidic devices and circuits for neuromorphic computing, the results also shed light on the development of field-assisted ion-selection-membrane filtration techniques as well as the investigations of large neurons and giant synapses. Further work is needed to de-embed parasitic components of the measurement setup to obtain intrinsic large memristor properties. Full article

The mechanism by which voltage-gated ion channels open and close has been the subject of intensive investigation for decades. For a large class of potassium channels and related sodium channels, the consensus has been that the gating current preceding the main ionic current is a large movement of positively charged segments of protein from voltage-sensing domains that are mechanically connected to the gate through linker sections of the protein, thus opening and closing the gate. We have pointed out that this mechanism is based on evidence that has alternate interpretations in which protons move. Very little literature considers the role of water and protons in gating, although water must be present, and there is evidence that protons can move in related channels. It is known that water has properties in confined spaces and at the surface of proteins different from those in bulk water. In addition, there is the possibility of quantum properties that are associated with mobile protons and the hydrogen bonds that must be present in the pore; these are likely to be of major importance in gating. In this review, we consider the evidence that indicates a central role for water and the mobility of protons, as well as alternate ways to interpret the evidence of the standard model in which a segment of protein moves. We discuss evidence that includes the importance of quantum effects and hydrogen bonding in confined spaces. K⁺ must be partially dehydrated as it passes the gate, and a possible mechanism for this is considered; added protons could prevent this mechanism from operating, thus closing the channel. The implications of certain mutations have been unclear, and we offer consistent interpretations for some that are of particular interest. Evidence for proton transport in response to voltage change includes a similarity in sequence to the H_v1 channel; this appears to be conserved in a number of K⁺ channels. We also consider evidence for a switch in -OH side chain orientation in certain key serines and threonines. Full article

Alkaline electrolytic water hydrogen generation, a key driver in the growth of hydrogen energy, heavily relies on high-efficiency and high-purity ion exchange membranes. In this study, three-dimensional (3D) wrinkled reduced graphene oxide (WG) nanosheets obtained through a simple thermal reduction process and two-dimensional (2D) graphene oxide act as building blocks, with ethylenediamine as a crosslinking stabilizer, to construct a unique 3D/2D 2 nm-tunneling structure between the GO and WG sheets through via an amide connection at a WG/GO ratio of 1:1. Here, the wrinkled graphene (WG) undergoes a transition from two-dimensional (2D) graphene oxide (GO) into three-dimensional (3D) through the adjustment of surface energy. By increasing the interlayer spacing and the number of ion fluid channels within the membranes, the E-W/G membrane has achieved the rapid passage of hydroxide ions (OH⁻) and simultaneous isolation of produced gas molecules. Moreover, the dense 2 nm nano-tunneling structure in the electrolytic water process enables the E-W/G membrane to attain current densities >99.9% and an extremely low gas crossover rate of hydrogen and oxygen. This result suggests that the as-prepared membrane effectively restricts the unwanted crossover of gases between the anode and cathode compartments, leading to improved efficiency and reduced gas leakage during electrolysis. By enhancing the purity of the hydrogen production industry and facilitating the energy transition, our strategy holds great potential for realizing the widespread utilization of hydrogen energy. Full article

Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies. Full article

Background: The reproducibility of research findings continues to be a challenge in many fields, including neurosciences. It is now required that biological variables such as sex and age be considered in preclinical and clinical research. Rodents are frequently used to model clinical conditions; however, litter information is rarely presented. Some studies utilize entire litters with each animal treated as an independent sample, while others equally assign animals from each litter to different groups/treatments, and others use averaged data. These methods can yield different results. Methods: This study used different analysis methods to evaluate embryo and placenta weights from E17.5 acid-sensing ion channel 2a (ASIC2a) mice with or without seizure exposure. Results: When each embryo was treated as an individual sample, fetal and placental weight significantly differed following seizures in the ASIC2a heterozygous (+/−) and homozygous (−/−) groups. Differences in fetal weight were driven by females in the ASIC2a+/− group and both sexes in the ASIC2a−/− group. These differences were lost when an average per sex/genotype/litter was used. There was no difference in placental weight when treated individually; however, female ASIC2a−/− placentas weighed less following seizures. This difference was lost with averaged data. ASIC2a−/− fetuses from −/− dams had reduced weights post-seizure exposure. Position on the uterine horn influenced embryo and placental weight. Conclusions: Our results indicate that using full litters analyzed as individual data points should be avoided, as it can lead to Type I errors. Furthermore, studies should account for litter effects and be transparent in their methods and results. Full article