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Effects of sulfide and polysulfides transmitted by direct or signal transduction-mediated activation of TRPA1 channels.

Hydrogen sulfide (H2 S) is a gaseous mediator in various physiological and pathological processes, including neuroimmune modulation, metabolic pathways, cardiovascular system, tumour growth, inflammation and pain. Now the hydrogen polysulfides (H2 Sn ) have been recognised as signalling molecules modulating ion channels, transcription factors and protein kinases. Transient receptor potential (TRP) cation channels can be activated by mechanical, thermal or chemical triggers. Here, we review the current literature regarding the biological actions of sulfide and polysulfide compounds mediated by …

Challenging the catechism of therapeutics for chronic neuropathic pain: Targeting CaV2.2 interactions with CRMP2 peptides.

Chronic neuropathic pain management is a worldwide concern. Pharmaceutical companies globally have historically targeted ion channels as the therapeutic catechism with many blockbuster successes. Remarkably, no new pain therapeutic has been approved by European or American regulatory agencies over the last decade. This article will provide an overview of an alternative approach to ion channel drug discovery: targeting regulators of ion channels, specifically focusing on voltage-gated calcium channels. We will highlight the discovery of an anti-nociceptive peptide derived from a novel calcium c…

The Effects of Buthotus schach Scorpion Venom on Electrophysiological Properties of Magnocellular Neurons of Rat Supraoptic Nucleus.

Bothutous Schach (BS) scorpion venom consists of several polypeptides that could modulate ion channels. In this study, the effects of BS crude venom on passive and active electrophysiological properties of rat neurons in supraoptic nucleus (SON) of hypothalamus was investigated using whole-cell patch clamp technique. The results showed that bath application of BS venom produced significant change in passive properties of SON neurons, namely a decrease in resting membrane potential and an increase in input resistance of the cells. Also, significant change in active properties of SON neurons was…

Asymmetry of Rb+ conduction emerged under bi-ionic conditions in epithelial maxi-K+ channels.

K(+) channels permit more than one ion within their conducting pathway at any given moment and show a saturating single-file behavior. The conduction of Rb(+) shows an unusual behavior, a so-called "Rb(+) anomaly," and it has been used to probe the mechanism of the ion conduction through K(+)-selective channels. Under the bi-ionic condition of K(+) and Rb(+), we carried out patch-clamp single-channel current measurements in MaxiK(+) channels from mouse submandibular acinar cells. Keeping only K(+) on one side of the membrane while varying fractional Rb(+) concentration on the opposite, we had

Виропорины вируса Мпокс.

Вирус Mpox или обезьянопокс (MPXV) относится к подклассу Poxviridae и недавно стал глобальной угрозой. С учетом ограниченного количества противовирусных препаратов, доступных для этого нового вида вирусов, трудно предотвратить болезнь, которую он вызывает. Поэтому определение новых целей в области борьбы с вирусом может оказаться выгодным для сдерживания этого заболевания. Поскольку каналы как семья являются отличными целями для наркотиков, мы стремимся определить вирусные иональные каналы для этого вируса, которые играют важную роль в создании каналов блокировки антивирусных препаратов. Анали

Совпадение в аннотации оригинала
Mpox or monkeypox virus (MPXV) belongs to the subclass of Poxviridae and has emerged recently as a global threat. With a limited number of a … he disease. Since channels as a family are excellent drug targets, we have sought to identify viral ion channels for this virus, which are instrumental in formulating channel-blocking anti-viral drugs. Bioinformatics analyses yielded eight transmembranous proteins smaller or equal to 100 amino acids in length. Subsequently, three independent bacteria-based ass …

Small Molecule Channels Harness Membrane Potential to Concentrate Potassium in trk1Δtrk2Δ Yeast.

Many protein ion channels harness membrane potential to move ions in opposition to their chemical gradient. Deficiencies of such proteins cause several human diseases, including cystic fibrosis, Bartter Syndrome, and proximal renal tubular acidosis. Using yeast as a eukaryotic model system, we asked whether, in the context of a protein ion channel deficiency in vivo, small molecule channels could similarly harness membrane potential to concentrate ions. Trk potassium transporters use membrane potential to move potassium from a relatively low concentration outside cells (∼15 mM) to one of >10× …

Sperm motility modulated by Trpv1 regulates zebrafish fertilization.

By responding to environmental and intracellular stimuli, ion channels play critical roles in sperm function regulation. Although the importance of ion channel in male reproduction has drawn increasing attention in many species, the knowledge about ion channels in zebrafish sperm is limited. Here, we show zebrafish sperm motility could be suppressed by general calcium channel blockers rather than by general potassium channel blockers. Further investigation found that sperm motility was not only suppressed by antagonist for the transient receptor potential vanilloid channel, subtype 1 (Trpv1), …

Channelopathies: potassium-related periodic paralyses and similar disorders.

Channelopathy is a term used to describe clinical problems caused by disorders of membrane ion channels. Included in this disease category are certain types of periodic paralyses, ataxia, myotonia, migraine headache, epilepsy, nephrolithiasis, and long QT syndrome. This article briefly summarizes membrane ion channel structure and function and details several relatively common channelopathies. In hyperkalemic periodic paralysis, mutant skeletal muscle sodium channels fail to close completely after an action potential. This evokes two apparently opposite symptoms: myotonia (caused by a small de…

Calcium Channels in the Heart: Disease States and Drugs.

Calcium ions are the major signaling ions in the cells. They regulate muscle contraction, neurotransmitter secretion, cell growth and migration, and the activity of several proteins including enzymes and ion channels and transporters. They participate in various signal transduction pathways, thereby regulating major physiological functions. Calcium ion entry into the cells is regulated by specific calcium channels and transporters. There are mainly six types of calcium channels, of which only two are prominent in the heart. In cardiac tissues, the two types of calcium channels are the L type a…

Electrophysiological characterization of a schistosome transient receptor potential channel activated by praziquantel.

Ion channels have proved to be productive targets for anthelmintic chemotherapy. One example is the recent discovery of a parasitic flatworm ion channel targeted by praziquantel (PZQ), the main clinical therapy used for treatment of schistosomiasis. The ion channel activated by PZQ - a transient receptor potential ion channel of the melastatin subfamily, named TRPMPZQ - is a Ca2+-permeable ion channel expressed in all parasitic flatworms that are PZQ-sensitive. However, little is currently known about the electrophysiological properties of this target that mediates the deleterious action of PZ…

Voltage-gated Ca(2+) channel mediated Ca(2+) influx in epileptogenesis.

Voltage- and ligand-gated ion channels are key elements in the etiopathogenesis of various forms of epilepsy. In this chapter, we present an overview of the functional implications of voltage-gated Ca(2+) channels in modulating internal Ca(2+) level fluctuations and generating ictiform/epileptiform cellular electrophysiological activity. A specific focus will be on the fascinating and evolving field of high-voltage activated (HVA) Non-L-type Ca(v)2.3 R-type channels and low-voltage activated (LVA) Ca(v)3.1-3.3 T-type Ca(2+) channels in the genesis of plateau potentials and excessive rebound bu…

Jingzhaotoxin-X, a gating modifier of Kv4.2 and Kv4.3 potassium channels purified from the venom of the Chinese tarantula Chilobrachys jingzhao.

BACKGROUND: The tarantula Chilobrachys jingzhao is one of the largest venomous spiders in China. In previous studies, we purified and charac … Kv4.3 potassium channels in a concentration- and voltage-dependent manner, without affecting other ion channels (Kv1.1, 1.2, 1.3, 2.1, delayed rectifier potassium channels, high- and low-voltage-activated Ca2+ channels, and voltage-gated sodium channels Nav1.5 and 1.7). JZTX-X also shifted the voltage-dependent channel activation to more depolarized potential …

Spontaneous Transition between Multiple Conductance States and Rectifying Behaviors in an Artificial Single-Molecule Funnel.

It has long been an aspirational goal to create artificial channel structures that replicate the feat achieved by ion channel proteins. Biological ion channels occasionally demonstrate multiple conductance states (known as subconductance), remaining a challenging property to achieve in artificial channel molecules. We report a funnel-shaped single-molecule channel constructed by an electron-deficient macrocycle and two electron-deficient aromatic imide arms. Planar lipid bilayer measurements reveal distinct current recordings, including a closed state, two conducting states, and spontaneous tr…

T-type channels in the sino-atrial and atrioventricular pacemaker mechanism.

Cardiac automaticity is a fundamental physiological function in vertebrates. Heart rate is under the control of several neurotransmitters and hormones and is permanently adjusted by the autonomic nervous system to match the physiological demand of the organism. Several classes of ion channels and proteins involved in intracellular Ca(2+) handling contribute to pacemaker activity. Voltage-dependent T-type Ca(2+) channels are an integral part of the complex mechanism underlying pacemaking. T-type channels also contribute to impulse conduction in mice and humans. Strikingly, T-type channel isofor…

Partners in Crime: Towards New Ways of Targeting Calcium Channels.

The characterization of calcium channel interactome in the last decades opened a new way of perceiving ion channel function and regulation. Partner proteins of ion channels can now be considered as major components of the calcium homeostatic mechanisms, while the reinforcement or disruption of their interaction with the channel units now represents an attractive target in research and therapeutics. In this review we will focus on the targeting of calcium channel partner proteins in order to act on the channel activity, and on its consequences for cell and organism physiology. Given the recent …

Aberrant Expression of Sodium-Potassium-Chloride Cotransporter in Endometriosis.

Cell membrane ion channels have important roles in cell migration during cancer development and metastasis. Although endometriosis is a benign gynecological disease, some migration and invasion characteristics of endometriosis are similar to those of cancer. However, only a few studies have examined cell membrane ion channels and their associations with endometriosis. This study aimed to investigate the effects of these ion channels on development of endometriosis. A total of 39 women who underwent laparoscopic ovarian cyst enucleation were included in the study population. Eutopic endometrium…

Investigating the interaction of Grammostola rosea venom peptides and model lipid bilayers with solid-state NMR and electron microscopy techniques.

Spider venom contains a number of small peptides that can control the gating properties of a wide range of ion channels with high affinity and specificity. These ion channels are responsible for coordination and control of many bodily functions such as transducing signals into sensory functions, smooth muscle contractions as well as serving as sensors in volume regulation. Hence, these peptides have been the topic of many research efforts in hopes that they can be used as biomedical therapeutics. Several peptides are known to control the gating properties of ion channels by involving the lipid…

Melatonin inhibits voltage-gated potassium KV4.2 channels and negatively regulates melatonin secretion in rat pineal glands.

Melatonin is synthesized in and secreted from the pineal glands and regulates circadian rhythms. Although melatonin has been reported to modulate the activity of ion channels in several tissues, its effects on pineal ion channels remain unclear. In the present study, the effects of melatonin on voltage-gated K+ (KV) channels, which play a role in regulating the resting membrane potential, were examined in rat pinealocytes. The application of melatonin reduced pineal KV currents in a concentration-dependent manner (IC50 = 309 µM). An expression analysis revealed that KV4.2 channels were highly …

Covalent Organic Framework Electrolytes for Solid-State Lithium Batteries: Designing Ion Highways for Next-Generation Energy Storage.

Covalent organic frameworks (COFs) are emerging as a programmable platform for solid electrolytes in solid-state lithium batteries, since their crystalline, periodically ordered nanochannels can be engineered to enable directional ion transport. These low-resistance pathways promote directional lithium-ion (Li+) migration through a narrower, more spatially ordered distribution of coordination environments, achieved via site-to-site hopping and/or guest-assisted vehicular motion within the channels. This review presents a design-oriented framework linking COF structural descriptors to ion-trans

Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors.

Glycine receptors (GlyR) are inhibitory Cys-loop ion channels that contribute to the control of excitability along the central nervous system (CNS). GlyR are found in the spinal cord and brain stem, and more recently they were reported in higher regions of the CNS such as the hippocampus and nucleus accumbens. GlyR are involved in motor coordination, respiratory rhythms, pain transmission, and sensory processing, and they are targets for relevant physiologic and pharmacologic modulators. Several studies with protein crystallography and cryoelectron microscopy have shed light on the residues an…