Результаты поиска

Fast desensitization of acetylcholine receptors induced by a spider toxin.

Nicotinic acetylcholine receptors (nAChRs) are members of the "cys-loop" ligand-gated ion channel superfamily that play important roles in both the peripheral and central system. At the neuromuscular junction, the endplate current is induced by ACh binding and nAChR activation, and then, the current declines to a small steady state, even though ACh is still bound to the receptors. The kinetics of nAChRs with high affinity for ACh but no measurable ion conductance is called desensitization. This adopted desensitization of nAChR channel currents might be an important mechanism for protecting cel

Трансцентральные рецепторы потенциальных каналов в качестве ключевых регуляторов нейроинфламмации в неврологических расстройствах: механистические понимания, терапевтические возможности и будущие направления.

КОЛИЧЕСТВО: Ионные каналы трансцентристского рецептора (TRP) - повсеместное семейство неселективных каналов катиона - широко выражаются в нервной системе, иммунной системе и периферийных тканях. Эти каналы служат критическими датчиками для обнаружения температуры, механических сил и химических стимулов, тем самым регулируя многочисленные физиологические и патологические процессы. За последнее десятилетие их ключевая роль в нейроиммунном перекрестке и подстрекательском сигнальном сигнале стала одним из ключевых направлений неврологических исследований.МЕТОДЫ: В Паббмеде был проведен всеобъемлющ

Совпадение в аннотации оригинала
BACKGROUND: Transient receptor potential (TRP) ion channels, a ubiquitous family of nonselective cation channels, are extensively expressed across the nervous system, immune system, and peripheral tissues. These channels serve as critical sensors for detecting temperature, mechanical forces, and chemical stimuli, thereby regulating numerous physiological and…

Involvement of TREK1 channels in the proliferation of human hepatic stellate LX-2 cells.

Activation of hepatic stellate cells (HSCs) causes hepatic fibrosis and results in chronic liver diseases. Although activated HSC functions are facilitated by an increase in the cytosolic Ca2+ concentration ([Ca2+]cyt), the pathophysiological roles of ion channels are largely unknown. In the present study, functional analyses of the two-pore domain K+ (K2P) channels, which regulate the resting membrane potential and [Ca2+]cyt, were performed using the human HSC line, LX-2. Expression analyses revealed that TREK1 (also known as KCNK2 and K2P2.1) channels are expressed in LX-2 cells. Whole-cell …

Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein.

RATIONALE: L-type Ca(2+) (Ca(V)1.2) channels shape the cardiac action potential waveform and are essential for excitation-contraction coupling in heart. A gain-of-function G406R mutation in a cytoplasmic loop of Ca(V)1.2 channels causes long QT syndrome 8 (LQT8), a disease also known as Timothy syndrome. However, the mechanisms by which this mutation enhances Ca(V)1.2-LQT8 currents and generates lethal arrhythmias are unclear. OBJECTIVE: To test the hypothesis that the anchoring protein AKAP150 modulates Ca(V)1.2-LQT8 channel gating in ventricular myocytes. METHODS AND RESULTS: Using a combi

Antiarrhythmic drugs inhibit the G-protein and K+ channels in the cultured thyroid cell line.

We examined the effects of antiarrhythmic drugs on the induction of cAMP by TSH (thyroid-stimulating hormone), using continuously cultured F … hyroid Gs-protein and thyroid K+ channels. Considering the close relationship between G-protein and ion channels in the cardiac cell membrane, these different effects of Group Ia and Group Ib antiarrhythmic drugs on G-proteins and K+ channels are of interest. Further investigation is necessary to clarify the relationship between thyroid G-proteins and thyroid …

Inducible over-expression of cardiac Nos1ap causes short QT syndrome in transgenic mice.

Recent evidence demonstrated that alterations in the QT interval duration on the ECG are not only determined by mutations in genes for ion channels, but also by modulators of ion channels. Changes in the QT interval duration beyond certain thresholds are pathological and can lead to sudden cardiac death. We here focus on the ion channel modulator nitric oxide synthase 1 adaptor protein (Nos1ap). Whole-cell patch-clamp measurements of a conditional transgenic mouse model exhibiting cardiac-specific Nos1ap over-expression revealed a Nos1ap-dependent increase of L-type calcium channel nitrosylati…

Pharmacology of PIEZO1 channels.

PIEZO1 is a eukaryotic membrane protein that assembles as trimers to form calcium-permeable, non-selective cation channels with exquisite capabilities for mechanical force sensing and transduction of force into effect in diverse cell types that include blood cells, endothelial cells, epithelial cells, fibroblasts and stem cells and diverse systems that include bone, lymphatics and muscle. The channel has wide-ranging roles and is considered as a target for novel therapeutics in ailments spanning cancers and cardiovascular, dental, gastrointestinal, hepatobiliary, infectious, musculoskeletal, n…

Neurite outgrowth from PC12 cells is enhanced by an inhibitor of mechanical channels.

GsMTx4, a peptide inhibitor for mechanosensitive ion channels (MSCs), promoted neurite outgrowth from PC12 cells in the presence of NGF in a dose-dependent manner between 5 and 100 microM peptide. Enhanced neurite growth required >12 h of peptide exposure in cells grown with NGF. Adsorption of GsMTx4 to serum proteins in the media lowered the free peptide concentration of 100 microM to a free concentration of 5 microM, a concentration shown to completely inhibit MSCs in the patch clamp assay. Outside-out patches from PC12 cells grown in NGF had mechanically activated cation channels that were …

Small-conductance calcium-activated potassium channels in the heart: expression, regulation and pathological implications.

Ca2+-activated K+ channels are critical to cellular Ca2+ homeostasis and excitability; they couple intracellular Ca2+ and membrane voltage c … function also depends upon complex trafficking and expression processes and associations with other ion channels or subunits from different SK subtypes. Atrial and ventricular clinical arrhythmogenesis may follow both increased or decreased SK expression through decreased or increased APD correspondingly accelerating and stabilizing re-entrant rotors or increa …

TMEM16A and TMEM16B channel proteins generate Ca2+-activated Cl- current and regulate melatonin secretion in rat pineal glands.

Pinealocytes regulate circadian rhythm by synthesizing and secreting melatonin. These cells generate action potentials; however, the contribution of specific ion channels to melatonin secretion from pinealocytes remains unclear. In this study, the involvement and molecular identity of Ca2+-activated Cl- (ClCa) channels in the regulation of melatonin secretion were examined in rat pineal glands. Treatment with the ClCa channel blockers, niflumic acid or T16Ainh-A01, significantly reduced melatonin secretion in pineal glands. After pineal K+ currents were totally blocked under whole-cell patch c…

Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.

Rheumatoid arthritis is a common autoimmune disease that results from the deposition of antibodies-autoantigens in the joints, leading to long-lasting inflammation. The main features of RA include cartilage damage, synovial invasion and flare-ups of intra-articular inflammation, and these pathological processes significantly reduce patients' quality of life. To date, there is still no drug target that can act in rheumatoid arthritis. Therefore, the search for novel drug targets has become urgent. Due to their unique physicochemical properties, calcium ions play an important role in all cellula

Совпадение в полном тексте источника
… Acid-sensing ion channels: Advances, questions and therapeutic opportunities Trends Neurosci. 2006 29 578 586 10.1016/j.tins.2006.06.014 16891000 66. Wemmie J.A. Taugher R.J. Kreple C.J. Acid-sensing ion channels in pain and disease Nat. Rev. … Acid-sensing ion channels 3: A potential therapeutic target for pain treatment in arthritis Mol. Biol. Rep. 2010 37 3233 3238 10.1007/s11033-009-9907-6 19885742 72. Yu G.M. Liu D. Yuan N. Liu B.H. Dual role of acid-sensing ion channels 3 in rheumatoid arthritis: Destruction or protection? …

Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 2: Functional and Molecular Properties of ASOR/PAC Channels and Their Roles in Cell Volume Dysregulation and Acidotoxic Cell Death.

For survival and functions of animal cells, cell volume regulation (CVR) is essential. Major hallmarks of necrotic and apoptotic cell death are persistent cell swelling and shrinkage, and thus they are termed the necrotic volume increase (NVI) and the apoptotic volume decrease (AVD), respectively. A number of ubiquitously expressed anion and cation channels play essential roles not only in CVR but also in cell death induction. This series of review articles address the question how cell death is induced or protected with using ubiquitously expressed ion channels such as swelling-activated anio…

Polystyrene nanoparticles activate ion transport in human airway epithelial cells.

BACKGROUND: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have th … ) channels by the nanoparticles. CONCLUSION: This is the first study to identify the activation of ion channels in airway cells after exposure to polystyrene-based nanomaterials. Thus, polystyrene nanoparticles cannot be considered as a simple neutral vehicle for drug delivery for the treatment of lung diseases, due to the fact that they may have the ability …

Apparent intermediate K conductance channel hyposmotic activation in human lens epithelial cells.

This study explores the nature of K fluxes in human lens epithelial cells (LECs) in hyposmotic solutions. Total ion fluxes, Na-K pump, Cl-dependent Na-K-2Cl (NKCC), K-Cl (KCC) cotransport, and K channels were determined by 85Rb uptake and cell K (Kc) by atomic absorption spectrophotometry, and cell water gravimetrically after exposure to ouabain +/- bumetanide (Na-K pump and NKCC inhibitors), and ion channel inhibitors in varying osmolalities with Na, K, or methyl-d-glucamine and Cl, sulfamate, or nitrate. Reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analyses, and imm

Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology.

The epithelium of the kidney collecting duct (CD) is composed mainly of two different types of cells with distinct and complementary functions. CD principal cells traditionally have been considered to have a major role in Na+ and water regulation, while intercalated cells (ICs) were thought to largely modulate acid-base homeostasis. In recent years, our understanding of IC function has improved significantly owing to new research findings. Thus, we now have a new model for CD transport that integrates mechanisms of salt and water reabsorption, K+ homeostasis, and acid-base status between princ

Non-NMDAR neuronal Ca(2+)-permeable channels in delayed neuronal death and as potential therapeutic targets for ischemic brain damage.

INTRODUCTION: Transient cerebral ischemia represents the most common cause of complex chronic disability in adults due to delayed neuronal death as a result of aberrant post-ischemic increases in the [Ca(2+)]c and [Zn(2+)]c. A number of Ca(2+)-permeable channels are engaged in transient ischemia-induced neuronal death. AREAS COVERED: In this review, the authors discuss the GluA2-lacking AMPARs, acid-sensing ion channel 1a, melastatin-related transient receptor potential 2 (TRPM2), TRPM7 and store-operated Ca(2+) channels expressed in ischemia-vulnerable neurons, and focus on the studies using

Spider-venom peptides that target voltage-gated sodium channels: pharmacological tools and potential therapeutic leads.

Voltage-gated sodium (Na(V)) channels play a central role in the propagation of action potentials in excitable cells in both humans and insects. Many venomous animals have therefore evolved toxins that modulate the activity of Na(V) channels in order to subdue their prey and deter predators. Spider venoms in particular are rich in Na(V) channel modulators, with one-third of all known ion channel toxins from spider venoms acting on Na(V) channels. Here we review the landscape of spider-venom peptides that have so far been described to target vertebrate or invertebrate Na(V) channels. These pept

Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.

BACKGROUND: Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital myopathies. The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of attacks in PP. OBJECTIVE: This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background. METHODS: We searched databases for randomized clinical tr

Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene.

BACKGROUND: Type-1 long-QT syndrome (LQTS) is caused by loss-of-function mutations in the KCNQ1-encoded I(Ks) cardiac potassium channel. We evaluated the effect of location, coding type, and biophysical function of KCNQ1 mutations on the clinical phenotype of this disorder. METHODS AND RESULTS: We investigated the clinical course in 600 patients with 77 different KCNQ1 mutations in 101 proband-identified families derived from the US portion of the International LQTS Registry (n=425), the Netherlands' LQTS Registry (n=93), and the Japanese LQTS Registry (n=82). The Cox proportional hazards sur