A5100330440- Ion channel regulation and function
- Ion Channels and Receptors
- Ion Transport and Channel Regulation
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Cardiac electrophysiology and arrhythmias
- Phytochemicals and Antioxidant Activities
- Herbal Medicine Research Studies
- Insect and Pesticide Research
- Neuroscience and Neural Engineering
- Venomous Animal Envenomation and Studies
- Respiratory and Cough-Related Research
- Cholinesterase and Neurodegenerative Diseases
- Congenital Diaphragmatic Hernia Studies
- Neurobiology and Insect Physiology Research
- Neonatal Respiratory Health Research
- Neuropeptides and Animal Physiology
- Bioactive Compounds and Antitumor Agents
Janssen (United States)
2010-2024
Wenzhou Medical University
2020
Springhouse
2010-2015
Janssen (Belgium)
2014
Johnson & Johnson (United States)
2011-2012
Massachusetts General Hospital
1994-1997
Harvard University
1997
Ion permeation through the nicotinic acetylcholine receptor channel is inhibited by general anesthetics. This inhibition could be mediated either binding of anesthetic molecules to protein itself or effects anesthetics on lipid environment protein.Patch clamp recording techniques were used investigate ether and propofol channels in outside-out patches from BC3H-1 cells. The kinetic conductance properties single measured. A rapid perfusion system was make changes concentration during patch...
Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that thermoresponsive to cool cold temperatures (8-28 °C) and also may be activated by chemical agonists such as menthol icilin. Antagonism of TRPM8 activation currently under investigation for the treatment painful conditions related cold, allodynia hyperalgesia. The design, synthesis, optimization class selective antagonists based on benzimidazole scaffold described, leading identification compounds...
A cone snail venom peptide, μO§-conotoxin GVIIJ from Conus geographus, has a unique posttranslational modification, S-cysteinylated cysteine, which makes possible formation of covalent tether peptide to its target Na channels at distinct ligand-binding site. is 35-aa with 7 cysteine residues; six the cysteines form 3 disulfide cross-links, and one (Cys24) S-cysteinylated. Due limited availability native GVIIJ, we primarily used synthetic analog whose Cys24 was S-glutathionylated (abbreviated...
Ion channels are an attractive class of drug targets, but progress in developing inhibitors for therapeutic use has been limited largely due to challenges identifying subtype selective small molecules. Animal venoms provide alternative source ion channel modulators, and the several species, such as scorpions, spiders snails, known be rich sources modulating peptides. Importantly, these peptides often bind hyper-variable extracellular loops, creating potential selectivity rarely achieved with...
Abstract Acid-sensing ion channels (ASICs) are proton-gated cation critical for neuronal functions. Studies of ASIC1, a major ASIC isoform and proton sensor, have identified acidic pocket, an extracellular region enriched in residues, as key participant channel gating. While binding to this by the venom peptide psalmotoxin modulates gating, molecular structural mechanisms gating modulation small molecules poorly understood. Here, combining functional, crystallographic, computational...
Reported herein is the design, synthesis, and pharmacologic characterization of a class TRPV1 antagonists constructed on benzo[d]imidazole platform that evolved from biaryl amide lead. This design composes three sections: 2-substituted 5-phenyl headgroup attached to platform, which tethered at two position phenyl tail group. Optimization this led identification 4 (mavatrep), comprising trifluoromethyl–phenyl–vinyl tail. In functional assay, using cells expressing recombinant human channels,...
Acid-Sensing Ion Channels (ASICs) are gated by extracellular protons and play important roles in physiological pathological states, such as pain stroke. ASIC1a ASIC2a, two of the most highly expressed subunits brain, form functional homo- hetero-meric (ASIC1a/2a) channels. The function has been widely studied using psalmotoxin (PcTx1), a venom-derived peptide, an ASIC1a-selective antagonist. Here, whole-cell patch clamp, we show that PcTx1 dual actions at ASIC1a/2a. It can either inhibit or...
Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in cell activation. Previous studies have shown blocking channels human during activation results reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore effects blockers response different subsets under various stimulation conditions. Our show that, unlike immune suppressor cyclosporine A, inhibitory effect partial strength dependent, with...
Pain is a significant public health burden in the United States, and current treatment approaches rely heavily on opioids, which often have limited efficacy can lead to addiction. In humans, functional loss of voltage-gated sodium channel Nav1.7 leads pain insensitivity without deficits central nervous system. Accordingly, discovery selective antagonist should provide an analgesic abuse liability improved side-effect profile. Huwentoxin-IV, component tarantula venom, potently blocks channels...
Abstract Voltage‐gated sodium (Na v ) channels are highly sensitive to membrane potential and have fast gating kinetics. Patch clamp electrophysiology has long been the gold standard for studying these channels. Combining high throughput with information content/accuracy, automated patch technologies emerged as critical tools in ion channel drug discovery. Described this unit is use of QPatch, one systems, study Na function pharmacology. Curr. Protoc. Pharmacol . 65:11.14.1‐11.14.45. © 2014...
Abstract To explore the effects of aquaporin (AQP) 1 on pregnancy outcome and association between expression AQP1 other AQPs in placenta foetal membranes, rate copulatory plugs pregnancy, amniotic fluid (AF) volume, osmolality composition were determined -knockout ( −/− ) mice at different gestational days (GD). The location membranes mice, AQP1-siRNA transfected WISH cells oligohydramnios patients also detected. Compared to control exhibited reduced copulation plug successful rates, but...
Abstract Acid-sensing ion channels (ASICs) are proton-gated cation widely expressed in the nervous system. ASIC gating is modulated by divalent cations as well small molecules; however, molecular determinants of modulation not understood. Previously, we identified two molecules that bind to ASIC1a at a novel site acidic pocket and modulate ASIC1 manner broadly resembling cations, raising possibility these may help illuminate cations. Here, examined how groups modulators might interact...
To explore the genetic basis for a child suspected hypokalemic periodic paralysis.Clinical data of patient was collected, and venous blood samples were taken from his parents extraction genomic DNA. Next generation sequencing (NGS) with target capture carried out to detect potential variants. Suspected variants validated by Sanger sequencing.The developed fatigue without obvious reason at age 15. Laboratory test revealed hypokalemia but normal serum magnesium. Genetic testing discovered that...
Abstract L-type calcium channels (LTCCs) are highly expressed in the heart and brain critical for cardiac neuronal functions. LTCC-blocking drugs have a long successful record clinic treating cardiovascular disorders. In contrast, establishment of their efficacy indications central nervous system remains challenging given tendency existing LTCC being functionally mechanistically more selective peripheral tissues. LTCCs vivo large macromolecular complexes consisting pore-forming subunit other...