Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium

A full-length clone coding for the rat alpha 7 nicotinic receptor subunit was isolated from an adult brain cDNA library and expressed in Xenopus oocytes. A significant proportion of the current through alpha 7-channels is carried by Ca2+. This Ca2+ influx then activates a Ca(2+)- dependent Cl- conductance, which is blocked by the chloride channel blockers niflumic and fluflenamic acid. Increasing the external NaCl concentration caused the reversal potentials for the alpha 7-channels and the Ca(2+)-dependent Cl- channels to be shifted in opposite directions. Under these conditions, agonist application activates a biphasic current with an initial inward current through alpha 7- channels followed by a niflumic acid- and fluflenamic acid-blockable outward current through Ca(2+)-dependent Cl- channels. A relative measure of the Ca2+ permeability was made by measuring the shift in the reversal potential caused by adding 10 mM Ca2+ to the external solution. Measurements made in the absence of Cl-, to avoid artifactual current through Ca(2+)-activated Cl- channels, indicate that alpha 7- homooligomeric channels have a greater relative Ca2+ permeability than the other nicotinic ACh receptors. Furthermore, alpha 7-channels have an even greater relative Ca2+ permeability than the NMDA subtype of glutamate receptors. High levels of alpha 7-transcripts were localized by in situ hybridization in the olfactory areas, the hippocampus, the hypothalamus, the amygdala, and the cerebral cortex. These results imply that alpha 7-containing receptors may play a role in activating calcium-dependent mechanisms in specific neuronal populations of the adult rat limbic system.

• Publication year

  1993

• Venue

  Journal of Neuroscience

• Publication date

  1993-02-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1523/JNEUROSCI.13-02-00596.1993PMID 7678857PMCID PMC6576637
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Calcium modulation and high calcium permeability of neuronal nicotinic acetylcholine receptors.

  1992influential reference
• Nicotinic receptors that bind alpha-bungarotoxin on neurons raise intracellular free Ca2+.

  1992cited by this paper
• Nicotinic receptors that bind α-bungarotoxin on neurons raise intracellular free ca2+

  1992cited by this paper
• Chloride transport blockers prevent N-methyl-D-aspartate receptor-channel complex activation.

  1992cited by this paper
• Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor

  1991cited by this paper
• Functional contribution of neuronal AChR subunits revealed by antisense oligonucleotides.

  1991cited by this paper
• Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors.

  1991cited by this paper
• Both alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors

  1991cited by this paper
• Functional architecture of the nicotinic acetylcholine receptor: from electric organ to brain.

  1991cited by this paper
• Calcium permeability of neuronal nicotinic acetylcholine receptor channels in PC12 cells.

  1991cited by this paper
• Calcium permeability of the nicotinic acetylcholine receptor: the single-channel calcium influx is significant

  1990influential reference
• Protein kinase recognition sequence motifs.

  1990cited by this paper
• Brain α-bungarotoxin binding protein cDNAs and MAbs reveal subtypes of this branch of the ligand-gated ion channel gene superfamily

  1990cited by this paper
• Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones.

  1990cited by this paper
• Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes.

  1990cited by this paper
• A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX.

  1990influential reference
• Construction of directional cDNA libraries enriched for full-length inserts in a transcription-competent vector.

  1989influential reference
• Distribution of alpha2, alpha3, alpha4, and beta2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: A hybridization histochemical study in the rat

  1989influential reference
• [125I]alpha-bungarotoxin binding marks primary sensory area developing rat neocortex.

  1989cited by this paper
• A complete protocol for in situ hybridization of messenger RNAs in brain and other tissues with radi

  1989cited by this paper
• The α-bungarotoxin receptor purified from a human neuroblastoma cell line: Biochemical and immunological characterization

  1989cited by this paper
• Characterization of the α-Bungarotoxin Binding Protein from PC12 Cells

  1988cited by this paper
• Electrophysiology of a chick neuronal nicotinic acetylcholine receptor expressed in Xenopus oocytes after cDNA injection.

  1988cited by this paper
• Distribution of nicotinic cholinergic receptors in the rat tel- and diencephalon: a quantitative receptor autoradiographical study using [3H]-acetylcholine, [alpha-125I]bungarotoxin and [3H]nicotine.

  1988cited by this paper
• Biochemistry of nicotinic acetylcholine receptors in the vertebrate brain.

  1988cited by this paper
• Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family.

  1987cited by this paper
• Postnatal Development of Cholinergic Enzymes and Receptors in Mouse Brain

  1987cited by this paper
• Permeation and block of N‐methyl‐D‐aspartic acid receptor channels by divalent cations in mouse cultured central neurones.

  1987cited by this paper
• The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors

  1987cited by this paper
• α‐Bungarotoxin Binds to Low‐Affinity Nicotine Binding Sites in Rat Brain

  1986cited by this paper
• alpha-Bungarotoxin binds to low-affinity nicotine binding sites in rat brain.

  1986cited by this paper
• Genetic analysis of nicotine-induced seizures and hippocampal nicotinic receptors in the mouse.

  1986cited by this paper
• Purification and characterization of the alpha-bungarotoxin binding protein from rat brain.

  1985cited by this paper
• Purification and characterization of the α-bungarotoxin binding protein from rat brain

  1985cited by this paper
• Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin

  1985cited by this paper
• Brain and muscle nicotinic acetylcholine receptors are different but homologous proteins.

  1985cited by this paper
• Agonists block currents through acetylcholine receptor channels.

  1984cited by this paper
• Chloride current induced by injection of calcium into Xenopus oocytes.

  1984cited by this paper
• The Rat Brain in Stereotaxic Coordinates

  1983cited by this paper
• A simple method for displaying the hydropathic character of a protein.

  1982cited by this paper
• Snake alpha-toxin effects on cholinergic and noncholinergic responses of Aplysia californica neurons

  1981cited by this paper
• Subunit Structure of α‐Bungarotoxin Binding Component in Mouse Brain

  1981cited by this paper
• The permeability of endplate channels to monovalent and divalent metal cations

  1980influential reference
• Immunological distinction between acetylcholine receptor and the alpha-bungarotoxin-binding component on sympathetic neurons.

  1977cited by this paper
• alpha-Bungarotoxin binding and cholinergic receptor function on a rat sympathetic nerve line.

  1977cited by this paper
• Use of a snake venom toxin to characterize the cholinergic receptor protein.

  1970cited by this paper
• A new method for predkting signal sequence cleavage sites

  year unknowncited by this paper

• The role of astrocytes in Alzheimer's disease: Pathophysiology, biomarkers, and therapeutic potential

  2026cites this paper
• Nicotinic acetylcholine receptors (nACh) in GtoPdb v.2025.3

  2025cites this paper
• Targeting Neuronal Alpha7 Nicotinic Acetylcholine Receptor Upregulation in Age-Related Neurological Disorders

  2025cites this paper
• The Functional Topology of Phenylpiperazinium Agonists and Antagonists on the Nicotinic Acetylcholine Receptor Landscape: Pointing the Way for Future Therapeutic Management of Inflammation and Neuropathic Pain.

  2025cites this paper
• Auricular Transcutaneous Vagus Nerve Stimulation Enhances Post‐Stroke Neurological and Cognitive Recovery in Mice by Suppressing Ferroptosis Through α7 Nicotinic Acetylcholine Receptor Activation

  2025cites this paper
• Chronic nicotine enhances object recognition memory via inducing long-term potentiation in the medial prefrontal cortex in mice.

  2025cites this paper
• Huperzine A attenuates epileptic seizures via enhancing dCA1-projecting septal cholinergic transmission

  2025cites this paper
• Dual Cholinergic Modulation in Dementia: Quinuclidine Carbamates Targeting Butyrylcholinesterase and α7 Nicotinic Receptor.

  2025cites this paper
• Functional expression and properties of the tick α6 homomeric nicotinic acetylcholine receptor in Xenopus laevis oocytes

  2025cites this paper
• Astrocyte-to-neuron H2O2 signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer’s disease model

  2025cites this paper
• Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion

  2025cites this paper
• Structural insights into the progressive recovery of α7 nicotinic acetylcholine receptor from nicotine-induced desensitization

  2025cites this paper
• α7 nicotinic acetylcholine receptor and depression: Mechanistic insights and therapeutic prospects.

  2025cites this paper
• The human‐specific nicotinic receptor subunit CHRFAM7A reduces α7 receptor function in human induced pluripotent stem cells‐derived and transgenic mouse neurons

  2024cites this paper
• Competitive Antagonism of Xylazine on α7 Nicotinic Acetylcholine Receptors and Reversal by Curcuminoids

  2024cites this paper
• New Alpha9 nAChR Ligands Based on a 5-(Quinuclidin-3-ylmethyl)-1,2,4-oxadiazole Scaffold.

  2024cites this paper
• Protein Painting Mass Spectrometry in the Discovery of Interaction Sites within the Acetylcholine Binding Protein

  2024cites this paper
• α7 Nicotinic Receptor Activation Mitigates Herpes Simplex Virus Type 1 Infection in Microglia Cells.

  2024cites this paper
• Adaptive remodeling of the stimulus-secretion coupling: Lessons from the 'stressed' adrenal medulla.

  2024cites this paper
• Pharmacology and molecular modeling studies of sulfoxaflor, flupyradifurone and neonicotinoids on the human neuronal α7 nicotinic acetylcholine receptor.

  2024cites this paper
• Cholinergic System Structure and Function Changes in Individuals with Down Syndrome During the Development of Alzheimer's Disease.

  2024cites this paper
• Structural mechanisms of α7 nicotinic receptor allosteric modulation and activation.

  2024cites this paper
• Evidence for a novel neuronal mechanism driving Alzheimer's disease, upstream of amyloid

  2024cites this paper
• Flupyradifurone activates DUM neuron nicotinic acetylcholine receptors and stimulates an increase in intracellular calcium through the ryanodine receptors.

  2024cites this paper
• Functions and pharmacology of α2β2 nicotinic acetylcholine receptors; in and out of the shadow of α4β2 nicotinic acetylcholine receptors.

  2024cites this paper
• Curcumin Mitigates Muscle Atrophy Potentially by Attenuating Calcium Signaling and Inflammation in a Spinal Nerve Ligation Model

  2024cites this paper
• The many enigmas of nicotine.

  2024cites this paper
• The calcium–calmodulin‐dependent protein kinase kinase inhibitor, STO‐609, inhibits nicotine‐induced currents and intracellular calcium increase in insect neurosecretory cells

  2024cites this paper
• Role of Neuronal Nicotinic Acetylcholine Receptors in Cannabinoid Dependence.

  2023cites this paper
• Nicotinic acetylcholine receptors in neurological and psychiatric diseases.

  2023cites this paper
• Brain Regulation of Cardiac Function during Hypoglycemia

  2023cites this paper
• Central Lancashire Online Knowledge (CLoK)

  2023cites this paper
• Emerging computational motifs: Lessons from the retina.

  2023cites this paper
• Target identification and validation of the alpha7 nicotinic acetylcholine receptor as a potential therapeutic target in retinal disease

  2023cites this paper
• Silent agonists for α7 nicotinic acetylcholine receptors.

  2023cites this paper
• A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder.

  2023cites this paper
• A cholinergic circuit that relieves pain despite opioid tolerance.

  2023cites this paper
• Nicotinic acetylcholine receptors (nACh) in GtoPdb v.2023.3

  2023cites this paper
• Differential Activation and Desensitization States Promoted by Non-canonical α7 nAChR Agonists

  2022cites this paper
• WHEN A TROPHIC PROCESS TURNS TOXIC: ALZHEIMER'S DISEASE AS AN ABERRANT RECAPITULATION OF A DEVELOPMENTAL MECHANISM.

  2022cites this paper
• Speculation on How RIC-3 and Other Chaperones Facilitate α7 Nicotinic Receptor Folding and Assembly

  2022cites this paper
• Trifluoro-icaritin alleviates chronic inflammatory pain through α7nAChR-mediated suppression of HMGB1/NF-κB signaling in the spinal cord of rats.

  2022cites this paper
• Chemistry, Biosynthesis and Pharmacology of Sarsasapogenin: A Potential Natural Steroid Molecule for New Drug Design, Development and Therapy

  2022cites this paper
• Differential interactions of resting, activated, and desensitized states of the α7 nicotinic acetylcholine receptor with lipidic modulators

  2022cites this paper
• The dependence of acetylcholine on dynamic changes in the membrane potential and an action potential during spike timing‐dependent plasticity induction in the hippocampus

  2022cites this paper
• Effects of Exercise Training on the Autonomic Nervous System with a Focus on Anti-Inflammatory and Antioxidants Effects

  2022cites this paper
• Dendritic spine membrane proteome and its alterations in autistic spectrum disorder.

  2022cites this paper
• Differential Activation and Desensitization States Promoted by Noncanonical α7 Nicotinic Acetylcholine Receptor Agonists

  2022cites this paper
• Biological determinants impact the neurovascular toxicity of nicotine and tobacco smoke: a pharmacokinetic and pharmacodynamic perspective.

  2022cites this paper
• Suppression of neuroinflammation by an allosteric agonist and positive allosteric modulator of the α7 nicotinic acetylcholine receptor GAT107

  2021cites this paper
• The Allosteric Activation of α7 nAChR by α-Conotoxin MrIC Is Modified by Mutations at the Vestibular Site

  2021cites this paper
• Nicotine Enhances Firing Activity of Layer 5 Pyramidal Neurons in the Medial Prefrontal Cortex through Inhibition of Kv7 Channels.

  2021cites this paper
• Nicotinic Acetylcholine Receptor α7 Subunit Is an Essential Regulator of Seizure Susceptibility

  2021cites this paper
• Cellular responses and functions of α7 nicotinic acetylcholine receptor activation in the brain: a narrative review

  2021cites this paper
• Alterations and interactions of subcortical modulatory systems in Alzheimer's disease.

  2021cites this paper
• Stable desensitization of α7 nicotinic acetylcholine receptors by NS6740 requires interaction with S36 in the orthosteric agonist binding site.

  2021cites this paper
• Aβ1-16 controls synaptic vesicle pools at excitatory synapses via cholinergic modulation of synapsin phosphorylation

  2021cites this paper
• Therapeutic Targeting of a7 Nicotinic Acetylcholine Receptors

  2021cites this paper
• Parallel Synaptic Acetylcholine Signals Facilitate Large Monopolar Cell Repolarization and Modulate Visual Behavior in Drosophila

  2021cites this paper
• Cholinergic feedback to bipolar cells contributes to motion detection in the mouse retina

  2021cites this paper
• Nicotinic acetylcholine receptors (nACh) in GtoPdb v.2021.3

  2021cites this paper
• Title page

  2021cites this paper
• The Hair Cell α9α10 Nicotinic Acetylcholine Receptor: Odd Cousin in an Old Family

  2021cites this paper
• Structure and gating mechanism of the α7 nicotinic acetylcholine receptor.

  2021cites this paper
• Marine-derived nicotinic receptor antagonist toxins: Pinnatoxins and alpha conotoxins

  2021cites this paper
• A novel effect of PDLIM5 in α7 nicotinic acetylcholine receptor upregulation and surface expression

  2021cites this paper
• Metaplastic Reinforcement of Long-Term Potentiation in Hippocampal Area CA2 by Cholinergic Receptor Activation

  2021cites this paper
• Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3

  2021cites this paper
• The human-specific duplicated α7 gene inhibits the ancestral α7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter release

  2021cites this paper
• Synaptic Components, Function and Modulation Characterized by GCaMP6f Ca2+ Imaging in Mouse Cholinergic Myenteric Ganglion Neurons

  2021cites this paper
• Differential signalling induced by α7 nicotinic acetylcholine receptors in hippocampal dentate gyrus in vitro and in vivo

  2021cites this paper
• Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development in Drosophila

  2021cites this paper
• Lead and Excitotoxicity

  2021cites this paper
• Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors

  2021cites this paper
• Recent Developments In Novel Antidepressants Targeting Ô±4ÔÂ22-Nicotinic Acetylcholine Receptors

  2021cites this paper
• Tri uoro-Icaritin Ameliorates Complete Freund’s Adjuvant-Induced In ammatory Pain by α7nAChR- Mediated Inhibition of HMGB1/NF-κB Signaling in the Spinal Cord of Rats

  2021cites this paper
• Nicotinic Acetylcholine Receptor Involvement in Inflammatory Bowel Disease and Interactions with Gut Microbiota

  2021cites this paper
• Sex Differences in the Nicotinic Acetylcholine Receptor System of Rodents: Impacts on Nicotine and Alcohol Reward Behaviors

  2021cites this paper
• Mechanism of calcium potentiation of the α7 nicotinic acetylcholine receptor

  2020cites this paper
• Nicotinic receptor pharmacology in silico: Insights and challenges.

  2020cites this paper
• The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse

  2020cites this paper
• Endogenous neurotoxin-like protein Ly6H inhibits alpha7 nicotinic acetylcholine receptor currents at the plasma membrane

  2020cites this paper
• Computational binding study with α7 nicotinic acetylcholine receptor of Anvylic-3288: an allosteric modulator

  2020cites this paper
• Molecular, physiological and behavioral characterization of the heterozygous Df[h15q13]/+ mouse model associated with the human 15q13.3 microdeletion syndrome.

  2020cites this paper
• Nicotinic Acetylcholine Receptors of PC12 Cells

  2020cites this paper
• Behavioral and Molecular Basis of Cholinergic Modulation of Pain: Focus on Nicotinic Acetylcholine Receptors.

  2020cites this paper
• Hippocampal Interneuronal α7 nAChRs Modulate Theta Oscillations in Freely Moving Mice.

  2020cites this paper
• Dopamine D3 Receptor Heteromerization: Implications for Neuroplasticity and Neuroprotection

  2020cites this paper
• Activators of α7 nAChR as Potential Therapeutics for Cognitive Impairment.

  2020cites this paper
• A Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders.

  2020cites this paper
• Design, synthesis, and electrophysiological evaluation of NS6740 derivatives: Exploration of the structure-activity relationship for alpha7 nicotinic acetylcholine receptor silent activation.

  2020cites this paper
• Cholinergic Receptors and Addiction.

  2020cites this paper
• Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalised Anxiety Disorder

  2020cites this paper
• Modulation of cholinergic activity through lynx prototoxins: Implications for cognition and anxiety regulation

  2020cites this paper
• Progress in nicotinic receptor structural biology.

  2020cites this paper
• Farnesyl Transferase Inhibitor Lonafarnib Enhances α7nAChR Expression Through Inhibiting DNA Methylation of CHRNA7 and Increases α7nAChR Membrane Trafficking

  2020cites this paper
• An α7-related nicotinic acetylcholine receptor mediates the ciliary arrest response in pharyngeal gill slits of Ciona

  2020cites this paper
• Chronic ethanol exposure potentiates cholinergic neurotransmission in the basolateral amygdala.

  2020cites this paper
• Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer’s Disease

  2020cites this paper
• Nicotinic Acetylcholine Receptors of PC12 Cells

  2020cites this paper