Результаты поиска

Targeting 5-HT2A receptors and Kv7 channels in PFC to attenuate chronic neuropathic pain in rats using a spared nerve injury model.

Chronic pain remains a disabling disease with limited therapeutic options. Pyramidal neurons in the prefrontal cortex (PFC) express excitatory Gq-coupled 5-HT2A receptors (5-HT2AR) and their effector system, the inhibitory Kv7 ion channel. While recent publications show these cells innervate brainstem regions important for regulating pain, the cellular mechanisms underlying the transition to chronic pain are not well understood. The present study examined whether local blockade of 5-HT2AR or enhanced Kv7 ion channel activity in the PFC would attenuate mechanical allodynia associated with spare

Update on Genetics of Primary Aldosteronism.

Primary aldosteronism (PA) is the most common form of secondary hypertension, with a prevalence of 5-10% among patients with hypertension. P … mechanism of excess aldosterone synthesis, particularly in APA. Most of the causative genes encode ion channels or pumps, and their mutations lead to depolarization of the cell membrane due to impairment of ion transport. Depolarization activates voltage-gated Ca2+ channels and intracellular calcium signaling and promotes the transcription of aldosterone synt …

[Molecular mechanisms underlying the pathogenesis of asthenospermia].

In recent years, male infertility has received more and more attention from scholars at home and abroad. Asthenospermia is one of the common causes of male infertility, the main manifestation of which is low sperm motility. Current studies show that the pathogenic factors for asthenospermia are complex and diverse, including gene mutations, alteration of ion channels, oxidative stress, changes in the contents of trace elements, and others. Despite the progress made in the related researches, the mechanisms underlying the pathogenesis of asthenospermia have not yet been fully elucidated. With a…

Expression of a potassium current in inner hair cells during development of hearing in mice.

Excitable cells use ion channels to tailor their biophysical properties to the functional demands made upon them. During development, these demands may alter considerably, often associated with a change in the cells' complement of ion channels. Here we present evidence for such a change in inner hair cells, the primary sensory receptors in the mammalian cochlea. In mice, responses to sound can first be recorded from the auditory nerve and observed behaviourally from 10-12 days after birth; these responses mature rapidly over the next 4 days. Before this time, mouse inner hair cells have slow v…

Regulation of arterial tone by activation of calcium-dependent potassium channels.

Blood pressure and tissue perfusion are controlled in part by the level of intrinsic (myogenic) vascular tone. However, many of the molecular determinants of this response are unknown. Evidence is now presented that the degree of myogenic tone is regulated in part by the activation of large-conductance calcium-activated potassium channels in arterial smooth muscle. Tetraethylammonium ion (TEA+) and charybdotoxin (CTX), at concentrations that block calcium-activated potassium channels in smooth muscle cells isolated from cerebral arteries, depolarized and constricted pressurized cerebral arteri

Evidence that tetrodotoxin and saxitoxin act at a metal cation binding site in the sodium channels of nerve membrane.

The effects of monovalent, divalent, and trivalent cations on the binding of tetrodotoxin and saxitoxin to intact nerves and to a preparation of solubilized nerve membranes have been examined. All eight divalent and trivalent cations tested, and the monovalent ions Li(+), Tl(+), and H(+) appear to compete reversibly with the toxins for their binding site. The ability of lithium to reduce toxin binding is paralleled by its ability to reduce tetrodotoxin-sensitive ion fluxes through the nerve membrane. We conclude that the toxins act at a metal cation binding site in the sodium channel and sugge

Emerging Perspectives on Pain Management by Modulation of TRP Channels and ANO1.

Receptor-type ion channels are critical for detection of noxious stimuli in primary sensory neurons. Transient receptor potential (TRP) channels mediate pain sensations and promote a variety of neuronal signals that elicit secondary neural functions (such as calcitonin gene-related peptide [CGRP] secretion), which are important for physiological functions throughout the body. In this review, we focus on the involvement of TRP channels in sensing acute pain, inflammatory pain, headache, migraine, pain due to fungal infections, and osteo-inflammation. Furthermore, action potentials mediated via …

Exploring mutation specific beta blocker pharmacology of the pathogenic late sodium channel current from patient-specific pluripotent stem cell myocytes derived from long QT syndrome mutation carriers.

The congenital long QT syndrome (LQTS), one of the most common cardiac channelopathies, is characterized by delayed ventricular repolarization underlying prolongation of the QT interval of the surface electrocardiogram. LQTS is caused by mutations in genes coding for cardiac ion channels or ion channel-associated proteins. The major therapeutic approach to LQTS management is beta blocker therapy which has been shown to be effective in treatment of LQTS variants caused by mutations in K+ channels. However, this approach has been questioned in the treatment of patients identified as LQTS variant…

IQM-PC332, a Novel DREAM Ligand with Antinociceptive Effect on Peripheral Nerve Injury-Induced Pain.

Neuropathic pain is a form of chronic pain arising from damage of the neural cells that sense, transmit or process sensory information. Given its growing prevalence and common refractoriness to conventional analgesics, the development of new drugs with pain relief effects constitutes a prominent clinical need. In this respect, drugs that reduce activity of sensory neurons by modulating ion channels hold the promise to become effective analgesics. Here, we evaluated the mechanical antinociceptive effect of IQM-PC332, a novel ligand of the multifunctional protein downstream regulatory element an…

Electrochemiluminescence on smartphone with silica nanopores membrane modified electrodes for nitroaromatic explosives detection.

Silica nanopores have electron channels and ion channels interpenetrating each other, which prompt the use of this structure for creating efficient electronic devices. In this study, silica nanopores membrane modified screen printed electrodes were applied in a smartphone-based electrochemiluminescence system for nitroaromatic explosives detection. Universal serial bus-on the go (USB-OTG) and camera on smartphone were used as the electrical stimulation and luminescence capture, respectively. ⎕Multimode methods including (red-green-blue) RGB, (hue-saturation-brightness) HSB, and Gray were propo…

Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone.

Failure of the ductus arteriosus (DA) to close at birth can lead to serious complications. Conversely, certain profound congenital cardiac m … ntifies subsets of genes that are enriched in the DA that may be used to develop DA-specific drugs. Ion channels that regulate DA tone, including BKCa channels, are promising targets. Specifically, BKCa channel agonists like NS1619 maintain DA patency even in the presence of O2 and may be clinically useful.

Lidocaine induces a slow inactivated state in rat skeletal muscle sodium channels.

1. Local anaesthetics such as lidocaine (lignocaine) interact with sodium channels in a manner that is exquisitely sensitive to the voltage-dependent conformational state of the ion channel. When depolarized in the presence of lidocaine, sodium channels assume a long-lived quiescent state. Although studies over the last decade have localized the lidocaine receptor to the inner aspect of the aqueous pore, the mechanistic basis of depolarization-induced 'use-dependent' lidocaine block remains uncertain. 2. Recent studies have shown that lowering the extracellular Na+ concentration ([Na+]o) and m

Atomistic simulation of voltage activation of a truncated BK channel.

Voltage-dependence gating of ion channels underlies numerous physiological and pathophysiological processes, and disruption of normal voltage gating is the cause of many channelopathies. Here, long timescale atomistic simulations were performed to directly probe voltage-induced gating transitions of the big potassium (BK) channels, where the voltage sensor domain (VSD) movement has been suggested to be distinct from that of canonical Kv channels but remains poorly understood. Using a Core-MT construct without the gating ring, multiple voltage activation transitions were observed at 750 mV, all…

Chlorpromazine directly inhibits Kv1.3 channels by facilitating the inactivation of channels.

Kv1.3 channels in microglia are pivotal in regulating neuroinflammation. The antipsychotic chlorpromazine (CPZ) demonstrates anti-inflammato … ts activation. Our findings suggest that CPZ directly blocks Kv1.3 channels without involving other ion channels or receptors, including dopamine receptors, thereby contributing to the understanding of its neuroinflammation-suppressing mechanism.

Alternative in vitro assays to assess the potency of sensory irritants-Is one TRP channel enough?

One important function of the peripheral nervous system is the detection of noxious chemicals in the environment as well as the recognition of tissue damage throughout the body. Transient receptor potential (TRP) ion channels are able to sense a multitude of signaling factors involved in these processes. Via the sensory ganglia these sentinels convey information to the central nervous system, where perceptions of nociception or sensory irritation are generated. From the 28 members of the 6 subfamilies present in mammals, researchers in toxicology paid special attention to TRPA1 and TRPV1 chann…

Напряжение и ингибиция 4-аминопиридина в канале Shaker Kv были выявлены с помощью модели закрытого состояния.

Создание и распространение потенциала действий у нейронов зависит от скоординированной активации зависящих от напряжения каналов натрия и калия. Семейство Kv1 (Shaker) каналов калия движет фазой реполяризации потенциала действия, открывая и закрывая их пору, процесс, контролируемый доменом датчика напряжения. Однако молекулярное описание того, как домен датчика напряжения движет поровым газом, было ограничено из-за отсутствия закрытых структур. Здесь мы представляем структурную модель закрытого канала Shaker, которая показывает структурную основу подкачивания напряжения. Используя метод конфор

Совпадение в аннотации оригинала
The generation and propagation of action potentials in neurons relies on the coordinated activation of voltage-dependent sodium and potassiu … thods used in this work will allow the characterization of conformational dynamics in voltage-gated ion channels, enabling drug design efforts focused on state-dependent modulation of ion channels for neurological disorders treatment.

High effectiveness of triptolide, an active diterpenoid triepoxide, in suppressing Kir-channel currents from human glioma cells.

Triptolide (Trip), a diterpene triepoxide isolated from medicinal vine Trypterygium wilfordii Hook. F. possessed multiple biological activities including antineoplastic actions. However, no report concerning its effects on ion currents has been published. In this study, we attempted to determine whether this compound has any effects on ion currents in malignant glioma cells. The mRNA expression of KCNJ10 (Kir4.1) was detected in U373 glioma cells. The inwardly rectifying K(+) currents (IK(IR)) in U373 cells were almost fully blocked by BaCl2 (1mM). Trip (30 nM-10 μM) effectively decreased the

Beyond Saline Electrolytes: Ultrafast and Selective Ion Transport in Gradient-Ordered Hydrogel Electrolytes Enables High-Rate and Ultra-Stable Energy Storage.

Aqueous ion batteries with traditional hydrogel electrolytes offer high safety, low cost, and simple manufacturing, but are hindered by slow ion transport, limiting fast charging applications. This study develops a gradient-ordered hydrogel (GO-hydrogel) electrolyte via centrifugal sieving. Through centrifugal shear and component design of sol, a gradient structure and a unilateral chain-ordered layer are created. This unique structure enables high-flux, high-rate ion transport and ion selectivity, achieving a conductivity of 53.34 mS cm-1. GO-hydrogel enables aqueous energy systems to outperf

Silver ions increase plasma membrane permeability through modulation of intracellular calcium levels in tobacco BY-2 cells.

Silver ions increase plasma membrane permeability for water and small organic compounds through their stimulatory effect on plasma membrane calcium channels, with subsequent modulation of intracellular calcium levels and ion homeostasis. The action of silver ions at the plant plasma membrane is largely connected with the inhibition of ethylene signalling thanks to the ability of silver ion to replace the copper cofactor in the ethylene receptor. A link coupling the action of silver ions and cellular auxin efflux has been suggested earlier by their possible direct interaction with auxin efflux