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Patch clamp nAChR

Hiroki Toyoda
The insular cortex is known to play a pivotal role in addiction to nicotine. Long-term depression (LTD) in the central nervous system is a major form of synaptic plasticity which is involved in learning and memory and in various pathological conditions such as nicotine addiction. Until now, effects of nicotine on LTD were mainly examined in the hippocampus and striatum, and there is no report showing the effects of nicotine on LTD in the insular cortex. In the present study, I show for the first time that nicotine facilitates LTD which is induced by combination of presynaptic stimulation with postsynaptic depolarization (paired training) in layer 5 pyramidal neurons of the mouse insular cortex using whole-cell patch-clamp recordings...
February 22, 2018: Neuroscience Letters
Lingqi Gao, Junde Han, Jie Bai, Jing Dong, Sen Zhang, Mazhong Zhang, Jijian Zheng
Early synchronized spontaneous network activity is a hallmark of the brain growth spurt period, during which general anesthetics cause widespread neuronal apoptosis and subsequent cognitive dysfunction. However, the relationship of such activity to anesthetic-induced neuronal apoptosis remains to be determined. In this study, we utilized patch-clamp electrophysiological recording, immunohistochemistry, and TUNEL assays to investigate the potential roles of spontaneous network activity in ketamine-induced neuronal apoptosis during early development...
February 7, 2018: Neuroscience
Yannong Dou, Jinque Luo, Xin Wu, Zhifeng Wei, Bei Tong, Juntao Yu, Ting Wang, Xinyu Zhang, Yan Yang, Xusheng Yuan, Peng Zhao, Yufeng Xia, Huijuan Hu, Yue Dai
BACKGROUND: Previous studies have demonstrated that oral administration of curcumin exhibited an anti-arthritic effect despite its poor bioavailability. The present study aimed to explore whether the gut-brain axis is involved in the therapeutic effect of curcumin. METHODS: The collagen-induced arthritis (CIA) rat model was induced by immunization with an emulsion of collagen II and complete Freund's adjuvant. Sympathetic and parasympathetic tones were measured by electrocardiographic recordings...
January 6, 2018: Journal of Neuroinflammation
Corinna Scheffel, Karin V Niessen, Sebastian Rappenglück, Klaus T Wanner, Horst Thiermann, Franz Worek, Thomas Seeger
Irreversible inhibition of acetylcholinesterase (AChE) resulting in accumulation of acetylcholine and overstimulation of muscarinic and nicotinic receptors accounts for the acute toxicity of organophosphorus compounds (OP). Accordingly, the mainstay pharmacotherapy against poisoning by OP comprises the competitive muscarinic acetylcholine receptor antagonist atropine to treat muscarinic effects and, in addition, oximes to reactivate inhibited AChE. A therapeutic gap still remains in the treatment of desensitized nicotinic acetylcholine receptors following OP exposure...
December 14, 2017: Toxicology Letters
Xiaorong Xu Parks, Donatella Contini, Paivi M Jordan, Joseph C Holt
In turtle posterior cristae, cholinergic vestibular efferent neurons (VENs) synapse on type II hair cells, bouton afferents innervating type II hair cells, and afferent calyces innervating type I hair cells. Electrical stimulation of VENs releases acetylcholine (ACh) at these synapses to exert diverse effects on afferent background discharge including rapid inhibition of bouton afferents and excitation of calyx-bearing afferents. Efferent-mediated inhibition is most pronounced in bouton afferents innervating type II hair cells near the torus, but becomes progressively smaller and briefer when moving longitudinally through the crista toward afferents innervating the planum...
2017: Frontiers in Cellular Neuroscience
Corinna Scheffel, Karin V Niessen, Sebastian Rappenglück, Klaus T Wanner, Horst Thiermann, Franz Worek, Thomas Seeger
Organophosphorus compounds, including nerve agents and pesticides, exert their toxicity through irreversible inhibition of acetylcholinesterase (AChE) resulting in an accumulation of acetylcholine and functional impairment of muscarinic and nicotinic acetylcholine receptors. Current therapy comprises oximes to reactivate AChE and atropine to antagonize effects induced by muscarinic acetylcholine receptors. Nicotinic malfunction leading to depression of the central and peripheral respiratory system is not directly treated calling for alternative therapeutic interventions...
November 27, 2017: Toxicology Letters
Cecilia Bouzat, Matías Lasala, Beatriz Elizabeth Nielsen, Jeremías Corradi, María Del Carmen Esandi
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels involved in many physiological and pathological processes. In vertebrates, there are seventeen different nAChR subunits that combine to yield a variety of receptors with different pharmacology, function, and localization. The homomeric α7 receptor is one of the most abundant nAChRs in the nervous system and it is also present in non-neuronal cells. It plays important roles in cognition, memory, pain, neuroprotection, and inflammation...
November 13, 2017: Journal of Physiology
Teagan R Wall, Brandon J Henderson, George Voren, Charles R Wageman, Purnima Deshpande, Bruce N Cohen, Sharon R Grady, Michael J Marks, Daniel Yohannes, Paul J Kenny, Merouane Bencherif, Henry A Lester
(E)-5-(Pyrimidin-5-yl)-1,2,3,4,7,8-hexahydroazocine (TC299423) is a novel agonist for nicotinic acetylcholine receptors (nAChRs). We examined its efficacy, affinity, and potency for α6β2(∗) (α6β2-containing), α4β2(∗), and α3β4(∗) nAChRs, using [(125)I]-epibatidine binding, whole-cell patch-clamp recordings, synaptosomal (86)Rb(+) efflux, [(3)H]-dopamine release, and [(3)H]-acetylcholine release. TC299423 displayed an EC50 of 30-60 nM for α6β2(∗) nAChRs in patch-clamp recordings and [(3)H]-dopamine release assays...
2017: Frontiers in Pharmacology
Sarah Y Sottile, Lynne Ling, Brandon C Cox, Donald M Caspary
KEY POINTS: Neuronal nicotinic acetylcholine receptors (nAChRs) play a fundamental role in the attentional circuitry throughout the mammalian CNS. In the present study, we report a novel finding that ageing negatively impacts nAChR efficacy in auditory thalamus, and this is probably the result of a loss of nAChR density (Bmax ) and changes in the subunit composition of nAChRs. Our data support the hypothesis that age-related maladaptive changes involving nAChRs within thalamocortical circuits partially underpin the difficulty that elderly adults experience with respect to attending to speech and other salient acoustic signals...
August 1, 2017: Journal of Physiology
Xujiao Zhou, Yun Cheng, Rong Zhang, Gang Li, Boqi Yang, Shenghai Zhang, Jihong Wu
Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists can prevent glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs). However, the neuroprotective effects and the mechanism of action of PNU-282987, an α7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly understood. We found that elevated intraocular pressure (IOP) downregulated retinal α7-nAChR expression. Electroretinography revealed that the amplitude of the photopic negative response (PhNR) decreased in parallel with the loss of RGCs caused by elevated IOP...
May 11, 2017: Scientific Reports
Saurabh Verma, Sudhanva Srinivas Kashyap, Alan Patrick Robertson, Richard John Martin
Many techniques for studying functional genomics of important target sites of anthelmintics have been restricted to Caenorhabditis elegans because they have failed when applied to animal parasites. To overcome these limitations, we have focused our research on the human nematode parasite Brugia malayi, which causes elephantiasis. Here, we combine single-cell PCR, whole muscle cell patch clamp, motility phenotyping (Worminator), and dsRNA for RNAi for functional genomic studies that have revealed, in vivo, four different muscle nAChRs (M-, L-, P-, and N-)...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
Monique J Windley, Irina Vetter, Richard J Lewis, Graham M Nicholson
κ-Hexatoxins (κ-HXTXs) are a family of excitotoxic insect-selective neurotoxins from Australian funnel-web spiders that are lethal to a wide range of insects, but display no toxicity towards vertebrates. The prototypic κ-HXTX-Hv1c selectively blocks native and expressed cockroach large-conductance calcium-activated potassium (BKCa or KCa 1.1) channels, but not their mammalian orthologs. Despite this potent and selective action on insect KCa 1.1 channels, we found that the classical KCa 1.1 blockers paxilline, charybdotoxin and iberiotoxin, which all block insect KCa 1...
December 2017: Neuropharmacology
Lucas C Armstrong, Glenn E Kirsch, Nikolai B Fedorov, Caiyun Wu, Yuri A Kuryshev, Abby L Sewell, Zhiqi Liu, Arianne L Motter, Carmine S Leggett, Michael S Orr
Nicotine, the addictive component of tobacco products, is an agonist at nicotinic acetylcholine receptors (nAChRs) in the brain. The subtypes of nAChR are defined by their α- and β-subunit composition. The α6β2β3 nAChR subtype is expressed in terminals of dopaminergic neurons that project to the nucleus accumbens and striatum and modulate dopamine release in brain regions involved in nicotine addiction. Although subtype-dependent selectivity of nicotine is well documented, subtype-selective profiles of other tobacco product constituents are largely unknown and could be essential for understanding the addiction-related neurological effects of tobacco products...
July 2017: SLAS Discovery
Huahua Sun, Yang Liu, Jian Li, Xinzhu Cang, Haibo Bao, Zewen Liu
The american cockroach (Periplaneta americana) dorsal unpaired median (DUM) neurons provide an native tool to analyze the functional and pharmacological properties of ion channels and membrane receptors, such as nicotine acetylcholine receptors (nAChRs). Here the imidacloprid-activated nAChR subtypes were examined in DUM neurons by the patch-clamp technique and the potential subunits involved in important subtypes were analyzed by combining with RNA interference (RNAi) technique. Imidacloprid exerted agonist activities on one subtype in α-Bgt-sensitive nAChRs and another subtype in α-Bgt-resistant nAChRs, in which the α-Bgt-resistant subtype showed much higher sensitivity to imidacloprid than the α-Bgt-sensitive subtype, with the difference close to 200-fold...
February 2017: Insect Biochemistry and Molecular Biology
Cristina Deflorio, Stéphane Blanchard, Maria Carla Carisì, Delphine Bohl, Uwe Maskos
Tobacco smoking is a public health problem, with ∼5 million deaths per year, representing a heavy burden for many countries. No effective therapeutic strategies are currently available for nicotine addiction, and it is therefore crucial to understand the etiological and pathophysiological factors contributing to this addiction. The neuronal α5 nicotinic acetylcholine receptor (nAChR) subunit is critically involved in nicotine dependence. In particular, the human polymorphism α5D398N corresponds to the strongest correlation with nicotine dependence risk found to date in occidental populations, according to meta-analysis of genome-wide association studies...
February 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Arik J Hone, J Michael McIntosh, Lola Rueda-Ruzafa, Juan Passas, Cristina de Castro-Guerín, Jesús Blázquez, Carmen González-Enguita, Almudena Albillos
Varenicline is a nicotinic acetylcholine receptor (nAChR) agonist used to treat nicotine addiction, but a live debate persists concerning its mechanism of action in reducing nicotine consumption. Although initially reported as α4β2 selective, varenicline was subsequently shown to activate other nAChR subtypes implicated in nicotine addiction including α3β4. However, it remains unclear whether activation of α3β4 nAChRs by therapeutically relevant concentrations of varenicline is sufficient to affect the behavior of cells that express this subtype...
January 2017: Journal of Neurochemistry
Glenn E Kirsch, Nikolai B Fedorov, Yuri A Kuryshev, Zhiqi Liu, Lucas C Armstrong, Michael S Orr
The Family Smoking Prevention and Tobacco Control Act of 2009 (Public Law 111-31) gave the US Food and Drug Administration (FDA) the responsibility for regulating tobacco products. Nicotine is the primary addictive component of tobacco and its effects can be modulated by additional ingredients in manufactured products. Nicotine acts by mimicking the neurotransmitter acetylcholine on neuronal nicotinic acetylcholine receptors (nAChRs), which function as ion channels in cholinergic modulation of neurotransmission...
August 2016: Assay and Drug Development Technologies
Marina Cholanian, Gregory L Powell, Richard B Levine, Ralph F Fregosi
Developmental nicotine exposure (DNE) is associated with increased risk of cardiorespiratory, intellectual, and behavioral abnormalities in neonates, and is a risk factor for apnea of prematurity, altered arousal responses and Sudden Infant Death Syndrome. Alterations in nicotinic acetylcholine receptor signaling (nAChRs) after DNE lead to changes in excitatory neurotransmission in neural networks that control breathing, including a heightened excitatory response to AMPA microinjection into the hypoglossal motor nucleus...
January 2017: Experimental Neurology
Silvia Corsini, Maria Tortora, Andrea Nistri
KEY POINTS: Impaired uptake of glutamate builds up the extracellular level of this excitatory transmitter to trigger rhythmic neuronal bursting and delayed cell death in the brainstem motor nucleus hypoglossus. This process is the expression of the excitotoxicity that underlies motoneuron degeneration in diseases such as amyotrophic lateral sclerosis affecting bulbar motoneurons. In a model of motoneuron excitotoxicity produced by pharmacological block of glutamate uptake in vitro, rhythmic bursting is suppressed by activation of neuronal nicotinic receptors with their conventional agonist nicotine...
November 15, 2016: Journal of Physiology
Weston A Nichols, Brandon J Henderson, Christopher B Marotta, Caroline Y Yu, Chris Richards, Dennis A Dougherty, Henry A Lester, Bruce N Cohen
A number of mutations in α4β2-containing (α4β2*) nicotinic acetylcholine (ACh) receptors (nAChRs) are linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), including one in the β2 subunit called β2V287L. Two α4β2* subtypes with different subunit stoichiometries and ACh sensitivities co-exist in the brain, a high-sensitivity subtype with (α4)2(β2)3 subunit stoichiometry and a low-sensitivity subtype with (α4)3(β2)2 stoichiometry. The α5 nicotinic subunit also co-assembles with α4β2 to form a high-sensitivity α5α4β2 nAChR...
2016: PloS One
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