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Ivermectin and its target molecules: shared and unique modulation mechanisms of ion channels and receptors by ivermectin.

Ivermectin (IVM) is an antiparasitic drug that is used worldwide and rescues hundreds of millions of people from onchocerciasis and lymphatic filariasis. It was discovered by Satoshi Ōmura and William C. Campbell, to whom the 2015 Nobel Prize in Physiology or Medicine was awarded. It kills parasites by activating glutamate-gated Cl- channels, and it also targets several ligand-gated ion channels and receptors, including Cys-loop receptors, P2X4 receptors and fernesoid X receptors. Recently, we found that IVM also activates a novel target, the G-protein-gated inwardly rectifying K+ channel, and…

Neuroprotective effects of inhibitors of Acid-Sensing ion channels (ASICs) in optic nerve crush model in rodents.

PURPOSE: The purpose of the current study was to assess the potential involvement of acid-sensing ion channel 1 (ASIC1) in retinal ganglion … tion. ABBREVIATIONS: 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF); acid-sensing ion channels (ASICs); analysis of variance (ANOVA); bicinchoninic acid (BCA); brain-derived neurotrophic factor (BDNF); central nervous system (CNS); ciliary neurotrophic factor (CNTF); dimethyl sulfoxide (DMSO); endoplasmic reticulum (ER); ethylene glycol-bis(β …

Properties of ATP-gated ion channels assembled from P2X2 subunits in mouse cochlear Reissner's membrane epithelial cells.

In the cochlea, Reissner's membrane separates the scala media endolymphatic compartment that sustains the positive endocochlear potential and ion composition necessary for sound transduction, from the scala vestibuli perilymphatic compartment. It is known that with sustained elevated sound levels, adenosine 5'-triphosphate (ATP) is released into the endolymph and ATP-gated ion channels on the epithelial cells lining the endolymphatic compartment shunt the electrochemical driving force, contributing to protective purinergic hearing adaptation. This study characterises the properties of epitheli…

Spontaneous formation of IpaB ion channels in host cell membranes reveals how Shigella induces pyroptosis in macrophages.

The Gram-negative bacterium Shigella flexneri invades the colonic epithelium and causes bacillary dysentery. S. flexneri requires the virulence factor invasion plasmid antigen B (IpaB) to invade host cells, escape from the phagosome and induce macrophage cell death. The mechanism by which IpaB functions remains unclear. Here, we show that purified IpaB spontaneously oligomerizes and inserts into the plasma membrane of target cells forming cation selective ion channels. After internalization, IpaB channels permit potassium influx within endolysosomal compartments inducing vacuolar destabilizati…

Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.

We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, related sodium and other sensory channels in human card…

Spinal cord plasticity and acid-sensing ion channels involvement in a rodent model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder characterized by intractable chronic abdominal pain. In this study, we examined the possible spinal mechanisms underlying colonic hypersensitivity (CHS) using a non-inflammatory rat model of IBS induced by rectal enemas of butyrate, a short-chain fatty acid. We hypothesized that spinal plasticity could be responsible for CHS and that ASIC channels, which are known to support pain-elicited currents in the spinal cord, could contribute to central sensitization in our model of IBS. First, in order to determine if vis

Нацеливание ионных каналов в неврологии и психиатрии: является ли фармакологическая беспорядочность препятствием или возможностью?

ЦЕЛЬ: Традиционный акцент на разработке высокоспециализированных фармацевтических препаратов ("магические пули") для лечения неврологических и психических расстройств ставится под сомнение формирующимися концепциями патофизиологии, в которых болезни рассматриваются как ненормальные взаимодействия в рамках сложных сетей молекулярных и клеточных компонентов. В так называемой сетевой фармакологии основное внимание уделяется изменению поведения целых систем, а не отдельных компонентов, что является терапевтической стратегией, в которой в идеале использовались бы единичные фармакологические агенты,

Совпадение в аннотации оригинала
BACKGROUND: The traditional emphasis on developing high specificity pharmaceuticals ("magic bullets") for the treatment of Neurological and … that illustrate the degree of promiscuity for GABA-, glycine-, serotonin-, and acetylcholine-gated ion channels, and 2) drug-centric maps that illustrated how characterization of promiscuity can guide drug development. IMPLICATIONS OF THE HYPOTHESIS: Developing promiscuity maps of approved neuro-pharmaceuticals will provide therapeutic class-based templates …

Epithelial ion channels in the regulation of female reproductive tract fluid microenvironment: implications in fertility and infertility.

An optimal fluid microenvironment in the female reproductive tract is considered to be crucial for successful reproductive events. Fluid absorption and secretion across the reproductive tract epithelia largely depends on electrolyte transport through the apically and basolaterally located ion channels, working together with an array of other transporters. This review will discuss the role of epithelial sodium channel (ENaC) and the cystic fibrosis transmembrane conductance regulator (CFTR) in regulating the fluid volume and composition of the reproductive tract and their importance in various …

Ion selectivity of porcine skeletal muscle Ca2+ release channels is unaffected by the Arg615 to Cys615 mutation.

The Arg615 to Cys615 mutation of the sarcoplasmic reticulum (SR) Ca2+ release channel of malignant hyperthermia susceptible (MHS) pigs results in a decreased sensitivity of the channel to inhibitory Ca2+ concentrations. To investigate whether this mutation also affects the ion selectivity filter of the channel, the monovalent cation conductances and ion permeability ratios of single Ca2+ release channels incorporated into planar lipid bilayers were compared. Monovalent cation conductances in symmetrical solutions were: Li+, 183 pS +/- 3 (n = 21); Na+, 474 pS +/- 6 (n = 29); K+, 771 pS +/- 7 (n

The role of ion channels and protein kinase C activation in the stimulation of complement protein synthesis.

Monocyte C2 synthesis is stimulated by antigen-antibody complexes (IC), carbamylcholine (C-Ch), phenylephrine (PE) and gamma-interferon. Tetrodotoxin or nifedipine abrogated the effects of IC, C-Ch and PE but did not influence the effect of gamma-interferon on C2 synthesis. Thus stimulation of C2 synthesis by IC, C-Ch and PE is dependent upon activation of Na+/K+ and Ca2+ channels, whereas gamma-interferon operates independently of these ion channels. Calcium channel agonists (CG28392 and BK8644) stimulated C2 synthesis, and this effect was prevented by nifedipine but not by tetrodotoxin. Thus…

Herpes simplex virus pUL56 abolishes neuronal activity by removing voltage-gated ion channels from the plasma membrane.

Herpes simplex virus 1 (HSV-1) infections of the central nervous system cause encephalitis and are associated with increased risk of neurode … itin-ligase adaptor pUL56 as the principal effector of this process: pUL56-dependent degradation of ion channels abolishes coordinated calcium signaling, whereas mutation of its E3-ligase-binding motifs preserves synchrony. Furthermore, expression of pUL56 alone is sufficient to abolish neuronal electrical activity. These findings establish pUL56 as a potent v …

Naltrexone attenuates airway remodeling by modulating neuromediators and sensory ion channels in cigarette smoke-induced COPD pathophysiology.

Chronic obstructive pulmonary disease (COPD) accompanied by inflammation contributes to airway obstruction, mucus hypersecretion, and other … holine, and dopamine) and upregulation of their respective receptors. Further the increased sensory ion channels (TRPV1 and TRPM8), indicating elevated neurogenic inflammation. Furthermore, COPD mice exhibited elevated fibrotic markers, including TGF-β1, α-SMA, MMP-2, and MMP-9, and TIMP-1 expression, collagen deposition, and mucus hypersecretion. NTX at low d …

PDOL polymeric protective layer with regulated ion migration channels enables ultrastable cycling of aqueous zinc metal anodes.

The practical deployment of aqueous zinc-ion batteries (AZIBs) is severely hindered by disordered zinc deposition and water-induced parasitic reactions, which degrade the long-term cycling stability of Zn anodes. Herein, a poly(1,3-dioxolane) (PDOL) protective layer is rationally constructed on the zinc surface via a facile one-step pre-polymerization strategy. The abundant ether oxygen sites of PDOL can strongly coordinate with Zn2+ to reorganize the solvation sheath, effectively weakening water competition and suppressing the hydrogen evolution reaction (HER). Meanwhile, the PDOL interlayer

The role of DHH motifs in PRUNE1 gene on ion channels: A new insight into epilepsy pathogenesis.

INTRODUCTION: PRUNE1-related disorders present diverse neurological manifestations, including developmental delay, congenital brain malformations, and epilepsy. Despite their frequency and often refractory nature, PRUNE1-related seizures have received insufficient attention. METHODS: Five Turkish patients carrying the homozygous c.316G>A (p.Asp106Asn) variant in the PRUNE1 gene were evaluated through retrospective review of clinical data, including neurological assessments, neuroimaging, and treatment responses. To explore the functional consequences of the mutation, computational structural

Bushen Huoxue recipe regulates endometrial epithelial ion channels to promote embryo implantation in controlled ovarian hyperstimulation mice.

BACKGROUND: Controlled ovarian hyperstimulation (COH) is commonly used to obtain large numbers of high-quality oocytes. However, elevated estrogen levels due to COH can disrupt uterine fluid metabolism and impair embryonic implantation. We investigated the effects and mechanisms of Bushen Huoxue recipe (BSHX) on COH-induced impairment of endometrial receptivity. METHODS: Female mice were randomly divided into the following five groups: control, model, BSHX-L, BSHX-M, and BSHX-H. In addition to the control group, the COH model was established by injecting mice in the other groups with 0.4 IU/g

Self-Assembled Ion Transport Channels in Block Copolymer Electrolytes for Dendrite-Free All-Solid-State Sodium Batteries.

Sodium metal batteries are a promising low-cost alternative to lithium-based systems, offering abundant raw materials and high energy density. However, their development is hindered by challenges such as dendrite growth and interfacial instability, which compromise safety and cycling performance. To address these issues, we report a new class of fluorinated, ion conducting block copolymer electrolytes designed to self-assemble into well-defined ion transport channels. These block copolymers, composed of perfluoropolyether (PFPE) segments and charged polyethylene oxide (PEO) blocks, self-assemb

The effect of triple CFTR modulator therapy and azithromycin on ion channels and inflammation in cystic fibrosis.

BACKGROUND: Inflammation in cystic fibrosis (CF) airways is difficult to treat with well-established regimens often including azithromycin (AZ) as an immunomodulatory drug. As AZ has been reported to require CF transmembrane conductance regulator (CFTR) to be able to reduce interleukin (IL)-8 and given the emergence of highly effective CFTR "triple" modulator therapy (elexacaftor/tezacaftor/ivacaftor; ETI), the aim of this study was to investigate the effect of AZ and ETI, singly and in combination, on ion channel activity and to assess the potential anti-inflammatory effects. METHODS: Electr

Synthetic anion channels: achieving precise mimicry of the ion permeation pathway of CFTR in an artificial system.

CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), a naturally occurring anion channel essential for numerous biological processes, possesses a positively charged ion conduction pathway within its transmembrane domain, which serves as the core module for promoting the movement of anions across cell membranes. In this study, we developed novel artificial anion channels by rebuilding the positively charged ion permeation pathway of the CFTR in artificial systems. These synthetic molecules can be efficiently inserted into lipid bilayers to form artificial ion channels, which exhibit a pr…

Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.

The blood-brain barrier (BBB) plays a critical role in maintaining ion and fluid homeostasis, essential for brain metabolism and neuronal function. Regulation of nutrient, water, and ion transport across the BBB is tightly controlled by specialized ion transporters and channels located within its unique cellular components. These dynamic transport processes not only influence the BBB's structure but also impact vital signaling mechanisms, essential for its optimal function. Disruption in ion, pH, and fluid balance at the BBB is associated with brain pathology and has been implicated in various

Opioids-induced inhibition of HERG ion channels and sudden cardiac death, a systematic review of current literature.

BACKGROUND: It is estimated that over 60 million individuals regularly use opioids globally, with opioid use disorder increasing substantially in the past decade. Several reports have linked sudden cardiac death, QTc prolongation, and other adverse cardiovascular outcomes with opioid use through their inhibitory effect on the human ether-a-go-go-related gene (HERG) ion channel. Therefore, understanding this underlying mechanism may be critical for risk prevention and management in prescribing opioids and treating patients with opioid dependency. AIM: The present systematic review summarizes t