ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1997
Mutation causing autosomal dominant nocturnal frontal lobe epilepsy alters Ca2+ permeability, conductance, and gating of human alpha4beta2 nicotinic acetylcholine receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 232 citations in OpenAlex.
- Autism Spectrum Disorder and Epilepsy: Pathogenetic Mechanisms and Therapeutic Implications.Journal of clinical medicine · 2025Review
- Can rodent models elucidate the pathomechanisms of genetic epilepsy?British journal of pharmacology · 2022Review
- Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons.Archives of toxicology · 2021Article
- Allosterically PotentiatedMolecular pharmacology · 2020Article
- Chrna5-Expressing Neurons in the Interpeduncular Nucleus Mediate Aversion Primed by Prior Stimulation or Nicotine Exposure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Unorthodox Acetylcholine Binding Sites Formed by α5 and β3 Accessory Subunits in α4β2* Nicotinic Acetylcholine Receptors.The Journal of biological chemistry · 2016Article
- Distinctive effects of nicotinic receptor intracellular-loop mutations associated with nocturnal frontal lobe epilepsy.Neuropharmacology · 2016Article
- Article
- Genetic neurological channelopathies: molecular genetics and clinical phenotypes.Journal of neurology, neurosurgery, and psychiatry · 2016Review
- A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit.The Journal of biological chemistry · 2015Article
- Heart failure induces changes in acid-sensing ion channels in sensory neurons innervating skeletal muscle.The Journal of physiology · 2015Article
- An Accessory Agonist Binding Site Promotes Activation of α4β2* Nicotinic Acetylcholine Receptors.The Journal of biological chemistry · 2015Article
- Functional Chimeras of GLIC Obtained by Adding the Intracellular Domain of Anion- and Cation-Conducting Cys-Loop Receptors.Biochemistry · 2015Article
- Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function.Neurology · 2015Article
- Cholinergic excitation in mouse primary vs. associative cortex: region-specific magnitude and receptor balance.The European journal of neuroscience · 2014Article
- Nocturnal frontal lobe epilepsy.Current neurology and neuroscience reports · 2014Review
- ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95.PloS one · 2014Article
- Effects of neuronal nicotinic acetylcholine receptor allosteric modulators in animal behavior studies.Biochemical pharmacology · 2013Review
- Article
- Acute activation, desensitization and smoldering activation of human acetylcholine receptors.PloS one · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A mutation (S247F) in the channel-lining domain (M2) of the alpha4 nicotinic acetylcholine receptor (AChR) subunit has previously been linked genetically to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). To better understand the functional significance of this mutation, we characterized the properties of mutant and wild-type human alpha4beta2 AChRs expressed in Xenopus oocytes. Both had similar expression levels and EC50 values for ACh and nicotine. Substantial use-dependent functional upregulation was found for mutant alpha4beta2 AChRs, but not for wild type. Mutant AChR responses showed faster desensitization, slower recovery from desensitization, less inward rectification, and virtually no Ca2+ permeability as compared with wild-type alpha4beta2 AChRs. Addition of the alpha5 subunit restored Ca2+ permeability to the mutant alpha4beta2alpha5 AChRs. At -80 mV, wild-type alpha4beta2 AChR single channel currents exhibited two conductances, each with two mean open times (gamma1 = 17 pS, tau1 = 3.7 msec, and tau2 = 23.4 msec; gamma2 = 28 pS, tau1 = 1.9 msec, and tau2 = 8.1 msec). In contrast, mutant AChRs exhibited only one conductance of 11 pS, with tau1 = 1.9 msec and tau2 = 4.1 msec. The net effect of the mutation is to reduce AChR function. This could result in the hyperexcitability characteristic of epilepsy if the mutant AChRs were part of an inhibitory circuit, e.g., presynaptically regulating the release of GABA. In the minority of AChRs containing the alpha5 subunit, the overall functionality of these AChRs could be maintained despite the mutation in the alpha4 subunit.
Indexed as
Identifiers
9364050PMC6573611W1673044943What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.