scholarly journals Increased nicotinic receptor desensitization in hypoglossal motor neurons following chronic developmental nicotine exposure

2012 ◽  
Vol 107 (1) ◽  
pp. 257-264 ◽  
Author(s):  
Jason Q. Pilarski ◽  
Hilary E. Wakefield ◽  
Andrew J. Fuglevand ◽  
Richard B. Levine ◽  
Ralph F. Fregosi
Keyword(s):  
Motor Neurons ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Upper Airway ◽  
Motor Nucleus ◽  
Nicotine Exposure ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Whole Cell Patch Clamp ◽  
Nachr Subtype ◽  
Inward Currents

Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed on hypoglossal motor neurons (XII MNs) that innervate muscles of the tongue. Activation of XII MN nAChRs evokes depolarizing currents, which are important for regulating the size and stiffness of the upper airway. Although data show that chronic developmental nicotine exposure (DNE) blunts cholinergic neurotransmission in the XII motor nucleus, it is unclear how nAChRs are involved. Therefore, XII MN nAChR desensitization and recovery were examined in tissues from DNE or control pups using a medullary slice preparation and tight-seal whole cell patch-clamp recordings. nAChR-mediated inward currents were evoked by brief pressure pulses of nicotine or the α4β2 nAChR agonist RJR-2403. We found that, regardless of treatment, activatable nAChRs underwent desensitization, but, following DNE, nAChRs exhibited increased desensitization and delayed recovery. Similar results were produced using RJR-2403, showing that DNE influences primarily the α4β2 nAChR subtype. These results show that while some nAChRs preserve their responsiveness to acute nicotine following DNE, they more readily desensitize and recover more slowly from the desensitized state. These data provide new evidence that chronic DNE modulates XII MN nAChR function, and suggests an explanation for the association between DNE and the incidence of central and obstructive apneas.

Expression of functional nicotinic acetylcholine receptors in neuroepithelial bodies of neonatal hamster lung

2003 ◽  
Vol 285 (6) ◽  
pp. L1203-L1212 ◽  
Author(s):  
Xiao Wen Fu ◽  
Colin A. Nurse ◽  
Suzanne M. Farragher ◽  
Ernest Cutz
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Respiratory Control ◽  
Hill Coefficient ◽  
Neuroepithelial Bodies ◽  
Patch Clamp Technique ◽  
Nicotinic Acetylcholine ◽  
Whole Cell Patch Clamp ◽  
Inward Currents ◽  
Double Label

Pulmonary neuroepithelial bodies (NEB) are presumed airway chemoreceptors involved in respiratory control, especially in the neonate. Nicotine is known to affect both lung development and control of breathing. We report expression of functional nicotinic acetylcholine receptors (nAChR) in NEB cells of neonatal hamster lung using a combination of morphological and electrophysiological techniques. Nonisotopic in situ hybridization method was used to localize mRNA for the β2-subunit of nAChR in NEB cells. Double-label immunofluorescence confirmed expression of α4-, α7-, and β2-subunits of nAChR in NEB cells. The electrophysiological characteristics of nAChR in NEB cells were studied using the whole cell patch-clamp technique on fresh lung slices. Application of nicotine (∼0.1-100 μM) evoked inward currents that were concentration dependent (EC50 = 3.8 μM; Hill coefficient = 1.1). ACh (100 μM) and nicotine (50 μM) produced two types of currents. In most NEB cells, nicotine-induced currents had a single desensitizing component that was blocked by mecamylamine (50 μM) and dihydro-β-erythroidine (50 μM). In some NEB cells, nicotine-induced current had two components, with fast- and slow-desensitizing kinetics. The fast component was selectively blocked by methyllcaconitine (MLA, 10 nM), whereas both components were inhibited by mecamylamine. Choline (0.5 mM) also induced an inward current that was abolished by 10 nM MLA. These studies suggest that NEB cells in neonatal hamster lung express functional heteromeric α3β2, α4β2, and α7 nAChR and that cholinergic mechanisms could modulate NEB chemoreceptor function under normal and pathological conditions.

scholarly journals Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii

2015 ◽  
Vol 113 (4) ◽  
pp. 1165-1174 ◽  
Author(s):  
Hong Xu ◽  
Jeffery A. Boychuk ◽  
Carie R. Boychuk ◽  
Victor V. Uteshev ◽  
Bret N. Smith
Keyword(s):  
Motor Neurons ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Fluorescent Protein ◽  
Gabaergic Neurons ◽  
Therapeutic Interventions ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Green Fluorescent

The caudal nucleus of the solitary tract (NTS) serves as the site of the first synapse for visceral sensory inputs to the central nervous system. The NTS sends functional projections to multiple brain nuclei, with gastric-related projections primarily targeting the dorsal motor nucleus of the vagus (DMV). Previous studies have demonstrated that the majority of caudal NTS neurons that project to the DMV respond robustly to nicotine and express nicotinic acetylcholine receptors (nAChRs). However, the cytochemical identity and relationship with specific viscera of DMV-projecting, nicotine-responsive caudal NTS neurons have not been determined. The present study used transgenic mice that express enhanced green fluorescent protein (EGFP) under a GAD67 promoter in a subset of GABAergic neurons, in vivo retrograde pseudorabies viral labeling to identify gastric-related vagal complex neurons, and patch-clamp electrophysiology in acute brain stem slices to test the hypothesis that gastric-related and GABAergic inhibitory synaptic input to the DMV from the caudal NTS is under a robust modulatory control by nAChRs. Our results suggest that activation of nAChRs in the caudal NTS, but not DMV, potentiates GABAergic, but not glutamatergic, input to the DMV. Gastric-related caudal NTS and DMV neurons are directly involved in this nicotine-sensitive circuitry. Understanding the central patterns of nicotinic modulation of visceral sensory-motor circuitry may help develop therapeutic interventions to restore autonomic homeostasis in patients with autonomic impairments.

scholarly journals Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice

2021 ◽  
Vol 22 (14) ◽  
pp. 7251
Author(s):  
Petrilla Jayaprakash ◽  
Dmytro Isaev ◽  
Waheed Shabbir ◽  
Dietrich E. Lorke ◽  
Bassem Sadek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Pathological Condition ◽  
Repetitive Behaviors ◽  
Social Deficits ◽  
Nicotinic Acetylcholine ◽  
Oxidative Stress Status ◽  
Inward Currents ◽  
Α7 Nachrs

Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Curcumin (CUR), the active compound of the spice turmeric, has been shown to act as a positive allosteric modulator of α7-nAChRs. Here we hypothesize that CUR, acting through α7-nAChRs, influences the neuropathology of ASD. In patch clamp studies, fast inward currents activated by choline, a selective agonist of α7-nAChRs, were significantly potentiated by CUR. Moreover, choline induced enhancement of spontaneous inhibitory postsynaptic currents was markedly increased in the presence of CUR. Furthermore, CUR (25, 50, and 100 mg/kg, i.p.) ameliorated dose-dependent social deficits without affecting locomotor activity or anxiety-like behaviors of tested male Black and Tan BRachyury (BTBR) mice. In addition, CUR (50 and 100 mg/kg, i.p.) mitigated oxidative stress status by restoring the decreased levels of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and the cerebellum of treated mice. Collectively, the observed results indicate that CUR potentiates α7-nAChRs in native central nervous system neurons, mitigates disturbed oxidative stress, and alleviates ASD-like features in BTBR mice used as an idiopathic rodent model of ASD, and may represent a promising novel pharmacological strategy for ASD treatment.

Potentiation and inhibition of subtypes of neuronal nicotinic acetylcholine receptors by Pb2+

1995 ◽  
Vol 291 (3) ◽  
pp. 399-406 ◽  
Author(s):  
Ruud Zwart ◽  
Regina G.D.M. Van Kleef ◽  
Jacob M. Milikan ◽  
Marga Oortgiesen ◽  
Henk P.M. Vijverberg
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine
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