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[Autoimmune channelopathies].

Autoimmune channelopathies are rare neuromuscular diseases that have been characterized clinically for several decades but for which the evidence of associated antibodies has only been recently demonstrated. Ion channels have an important role of activation, inhibition and regulation in neuromuscular transmission. Myasthenia gravis, generally associated with the presence of anti-acetylcholine receptor antibody, is the best-known channelopathy. Other anti-channel antibodies, including voltage-dependent, are associated with several neurological diseases, as illustrated by anti-voltage-gated calc…

Functional characterization of zebrafish Kcnh2a splice variants reveals distinct gating properties.

Zebrafish have emerged as an important vertebrate model for ion channel research. Human KCNH2 channels, commonly known as hERG channels, play critical roles in cardiac repolarization and are closely associated with inherited and acquired arrhythmia syndromes. In contrast, cardiac repolarization in zebrafish is primarily mediated by Kcnh6 channels, and the physiological properties of zebrafish Kcnh2 channels remain largely unknown. PCR analysis revealed that zebrafish kcnh2 is preferentially expressed in the brain, whereas kcnh6 is enriched in the heart, suggesting distinct physiological roles

Proton-selective conductance and gating of the lysosomal cation channel TMEM175.

The lysosomal cation channel TMEM175 plays a key role in luminal pH homeostasis and lysosome function, with aberrant activity linked to Parkinson's disease. Although initially described as a K+-selective channel, TMEM175 exhibits substantial H+ permeability. Here, we dissect complex changes affecting human TMEM175 conductance and ionic properties of TMEM175-mediated current in response to pH shifts on the luminal side of the protein. A drop in pH from 7.4 to 4.7 on the side equivalent to the lysosomal lumen triggers a sustained increase in TMEM175-mediated inward and outward currents, which is

Potential therapeutic targeting of BKCa channels in glioblastoma treatment.

Potassium channels in brain tissue orchestrate essential cellular processes, including the regulation of membrane potential and neuronal excitability. Among them, large-conductance calcium-activated potassium (BKCa) channels play a pivotal role in both normal brain physiology and the pathogenesis of glioblastoma multiforme, a highly aggressive primary brain tumor. Within the central nervous system, BKCa channels are widely expressed in neurons, astrocytes, and oligodendrocytes, contributing to ion homeostasis and synaptic transmission. In glioblastoma cells, overexpression of BKCa channels, pa

Transient receptor potential channels in hair follicle biology: physiological significance and translational relevance.

Transient receptor potential (TRP) channels are a family of versatile ion channels that act as sensor for a wide range of chemical and physical stimuli. These cation-permeable channels are widely expressed in various tissues and play pivotal roles in numerous biologic processes. Studies have demonstrated that six specific TRP channels -TRPV1, TRPV3, TRPV4, TRPM5, TRPML1 and TRPML3 - are actively involved in hair follicle (HF) cell proliferation, modulation of hair growth-related signalling pathways, regulation of hair cycle progression, and control of hair growth and pigmentation in humans and…

Hydration channel engineering in Tröger's base-POP membranes for mono/multivalent cation and anion discrimination.

Sustainable recovery of critical resources from complex aqueous streams is constrained by membranes that fail to combine rapid ion transport with precise mono/multivalent discrimination. Here, we report Tröger's base-derived porous organic polymer (POP) membranes with rigid, covalently crosslinked microporous frameworks that stabilize angstrom-scale transport channels while suppressing hydration-induced swelling. These membranes render rapid monovalent-ion transport with near-complete exclusion of multivalent cations and anions, including Mg2+, Al3+, SO42-, and PO43-. Experiments and simulatio

Photoisomerization of Azobenzene-Extended Charybdotoxin for the Optical Control of Kv1.2 Potassium Channel Activity.

Natural peptides from animal venoms effectively modulate ion channel activity. While photoswitches regulate small compound pharmacology, their application to natural peptides rich in disulfide bridges and active on ion channels is novel due to larger pharmacophores. A pilot study integrating azobenzene photoswitches into charybdotoxin (ChTx), known for blocking potassium channels is initiated. Two click-chemistry-compatible azobenzene are synthesized differing in length and amide orientation (Az1 & Az2). Az1 is grafted onto ChTx at various amino acid positions using L-azidohomoalanine mutation…

Механочувствительный канал Piezo1: новая цель в болезни обезвоживания.

Многие физиологические процессы в организме человека инициируются механическими сигналами, которые передаются по ионным каналам. Piezo-mechano-чувствительный ионный канал компонент 1 (Piezo1) — белок, ярко выраженный в мозгу и играющий решающую роль в зондировании изменений в механической микроокружающей среде. Широкие исследования показали, что Piezo1 является важным компонентом для генерирования токов в катионовых каналах с механическим приводом. Она участвует в ряде ключевых процессов в нервной системе, включая нейронное развитие и дифференциацию, регенерацию нервной системы, аксоновую орие

Совпадение в аннотации оригинала
Many physiological processes in the human body are initiated by mechanical signals, which are transmitted via ion channels. Piezo-type mechanosensitive ion channel component 1 (Piezo1) is a protein highly expressed in the brain, playing a critical role in sensing changes in the mechanical microenvironment. Extensive research has demonstrated that Piezo1 is a…

A bivalent remipede toxin promotes calcium release via ryanodine receptor activation.

Multivalent ligands of ion channels have proven to be both very rare and highly valuable in yielding unique insights into channel structure and pharmacology. Here, we describe a bivalent peptide from the venom of Xibalbanus tulumensis, a troglobitic arthropod from the enigmatic class Remipedia, that causes persistent calcium release by activation of ion channels involved in muscle contraction. The high-resolution solution structure of φ-Xibalbin3-Xt3a reveals a tandem repeat arrangement of inhibitor-cysteine knot (ICK) domains previously only found in spider venoms. The individual repeats of X…

Relevance of mitochondrial oxidative stress to arrhythmias: Innovative concepts to target treatments.

Cardiac arrhythmia occurs frequently worldwide, and in severe cases can be fatal. Mitochondria are the power plants of cardiomyocytes. In recent studies, mitochondria under certain stimuli produced excessive reactive oxygen species (ROS), which affect the normal function of cardiomyocytes through ion channels and related proteins. Mitochondrial oxidative stress (MOS) plays a key role in diseases with multifactorial etiopathogenesis, such as arrhythmia; MOS can lead to arrhythmias such as atrial fibrillation and ventricular tachycardia. This review discusses the mechanisms of arrhythmias caused…

Thermosensitive TRPV4 channels mediate temperature-dependent microglia movement.

Microglia maintain central nervous system homeostasis by monitoring changes in their environment (resting state) and by taking protective actions to equilibrate such changes (activated state). These surveillance and protective roles both require constant movement of microglia. Interestingly, induced hypothermia can reduce microglia migration caused by ischemia, suggesting that microglia movement can be modulated by temperature. Although several ion channels and transporters are known to support microglia movement, the precise molecular mechanism that regulates temperature-dependent movement of…

Molecular modification of a halohydrin dehalogenase for kinetic regulation to synthesize optically pure (S)-epichlorohydrin.

Asymmetric synthesis of chiral epichlorohydrin (ECH) from 1,3-dichloro-2-propanol (1,3-DCP) using halohydrin dehalogenases (HHDHs) is of great value due to the 100% theoretical yield and high enantioselectivity. The vital problem in the asymmetric synthesis is to prepare optically pure ECH. In this study, key amino acid residues located at halide ion channels of HheC (P175S/W249P) (HheCPS) were modified to regulate the kinetic parameters. HheCPS I81W, F86N and V94R were constructed with the corresponding halide ion channels destroyed. The catalytically efficiencies (kcat/Km) of the three mutan…

Goblet Cell Hyperplasia Requires High Bicarbonate Transport To Support Mucin Release.

Goblet cell hyperplasia, a feature of asthma and other respiratory diseases, is driven by the Th-2 cytokines IL-4 and IL-13. In human bronchial epithelial cells, we find that IL-4 induces the expression of many genes coding for ion channels and transporters, including TMEM16A, SLC26A4, SLC12A2, and ATP12A. At the functional level, we find that IL-4 enhances calcium- and cAMP-activated chloride/bicarbonate secretion, resulting in high bicarbonate concentration and alkaline pH in the fluid covering the apical surface of epithelia. Importantly, mucin release, elicited by purinergic stimulation, r…

Characterization of ion transport mechanisms involved in bombesin-stimulated biliary secretion in rat cholangiocytes.

BACKGROUND/AIMS: Bombesin is a neuropeptide which stimulates fluid and bicarbonate secretion from cholangiocytes by stimulating Cl-/HCO3- exchange. However, the underlying regulation and interactions of ion transporters and channels mediating this bombesin-stimulated biliary secretion are not well characterized. The aim of the study was to characterize the ion transport processes involved in bombesin-stimulated secretion in polarized cholangiocytes in comparison with those of secretin. METHODS: Isolated bile duct units (IBDU) were prepared from normal rat liver. Biliary secretion induced by b

The interaction of spider gating modifier peptides with voltage-gated potassium channels.

Gating modifier peptides bind to ion channels and alter the gating process of these molecules. One of the most extensively studied peptides, Hanatoxin (HaTx), isolated from a Chilean tarantula, has been used to characterize the blocking properties of the voltage-gated potassium channel Kv2.1. These studies have provided some insight into the gating mechanism in Kv channels. In this review we will discuss the interaction of HaTx and related spider peptides with Kv channels illustrating the properties of the binding surface of these peptides, their membrane partitioning characteristics, and will…

Calhm6 Governs Macrophage Polarization Through Chp1-Camk4-Creb1 Axis and Ectosomal Delivery in Inflammatory Responses.

Macrophage plasticity, critical for immune response, is often dysregulated in various infectious and inflammatory diseases. While ion channels have been implicated in immune cell modulation, how they influence macrophage polarization remains poorly understood. Here, it is demonstrated that ectosomes carrying the ion channel Calhm6 effectively suppress severe inflammation triggered by LPS. These Calhm6-bearing ectosomes, secreted by macrophages, facilitate M2-like polarization, elicit an anti-inflammatory response, and foster immune tolerance. Conversely, Calhm6 deficiency leads to suppressed C…

Precision medicine for long QT syndrome: patient-specific iPSCs take the lead.

Long QT syndrome (LQTS) is a detrimental arrhythmia syndrome mainly caused by dysregulated expression or aberrant function of ion channels. The major clinical symptoms of ventricular arrhythmia, palpitations and syncope vary among LQTS subtypes. Susceptibility to malignant arrhythmia is a result of delayed repolarisation of the cardiomyocyte action potential (AP). There are 17 distinct subtypes of LQTS linked to 15 autosomal dominant genes with monogenic mutations. However, due to the presence of modifier genes, the identical mutation may result in completely different clinical manifestations …

Novel pharmacological therapies for atrial fibrillation.

PURPOSE OF REVIEW: Atrial fibrillation is a common yet difficult cardiac rhythm to treat. Limitations of the currently available medications … harmacological research. RECENT FINDINGS: Novel ion channel blockers have targeted atrial-specific ion channels or a combination of ion channels in order to maximize efficacy and minimize proarrhythmic risk. Understanding of atrial fibrillation as a metabolically complex condition with activation of multiple signaling cascades has fuelled drug development in …

Stable expression of a functional homo-oligomeric Drosophila GABA receptor in a Drosophila cell line.

A cloned Drosophila gamma-aminobutyric acid GABA receptor subunit (Rdl) has been stably expressed as a functional homo-oligomeric ion channel in a Drosophila cell line. Stably-transfected clonal cell lines which expressed high levels of GABA receptor were identified by specific [3H]-muscimol binding. Expression of functional GABA-gated ion channels in these cell lines was demonstrated by electrophysiological recording. Rapid and pronounced rundown of responses to GABA during whole-cell patch clamp recordings was overcome by the inclusion of EGTA in the pipette solution, indicating a possible r…

A comprehensive review of HCN channel expression and Ih in the auditory system: then, now, and future perspectives.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel is highly specialized, mediating the flow of potassium and sodium ions when a cell is hyperpolarized. Since it was discovered nearly half a century ago, the HCN channel structure and function have been extensively characterized throughout the nervous system. This includes the auditory system, where HCN channels are abundantly expressed and are used to encode sound features with high temporal fidelity. Despite the ubiquitous presence of HCN channels in auditory regions, the physiological benefits of these channels within