ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2000
A molecular link between inward rectification and calcium permeability of neuronal nicotinic acetylcholine alpha3beta4 and alpha4beta2 receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
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- Functional expression and properties of the tick α6 homomeric nicotinic acetylcholine receptor inCurrent research in parasitology & vector-borne diseases · 2025Article
- Salmonella Typhimurium exploits host polyamines for assembly of the type 3 secretion machinery.PLoS biology · 2024Article
- DDAH1 promotes neurogenesis and neural repair in cerebral ischemia.Acta pharmaceutica Sinica. B · 2024Article
- Inhibition of nicotinic acetylcholine receptors by oligoarginine peptides and polyamine-related compounds.Frontiers in pharmacology · 2023Article
- Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway.Science advances · 2022Article
- Cholinergic feedback to bipolar cells contributes to motion detection in the mouse retina.Cell reports · 2021Article
- Nicotinic Acetylcholine Receptors of PC12 Cells.Cellular and molecular neurobiology · 2021Review
- Allosterically PotentiatedMolecular pharmacology · 2020Article
- Polyamine regulation of ion channel assembly and implications for nicotinic acetylcholine receptor pharmacology.Nature communications · 2020Article
- Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.Neuropharmacology · 2020Review
- Distinct Evolutionary Trajectories of Neuronal and Hair Cell Nicotinic Acetylcholine Receptors.Molecular biology and evolution · 2020Article
- Acetylcholine nicotinic receptor subtypes in chromaffin cells.Pflugers Archiv : European journal of physiology · 2018Review
- Impact of ageing on postsynaptic neuronal nicotinic neurotransmission in auditory thalamus.The Journal of physiology · 2017Article
- Targets of polyamine dysregulation in major depression and suicide: Activity-dependent feedback, excitability, and neurotransmission.Neuroscience and biobehavioral reviews · 2016Review
- Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function.Neurology · 2015Article
- Neuronal Nicotinic Acetylcholine Receptor Structure and Function and Response to Nicotine.International review of neurobiology · 2015Review
- Tracking the molecular evolution of calcium permeability in a nicotinic acetylcholine receptor.Molecular biology and evolution · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many nicotinic acetylcholine receptors (nAChRs) expressed by central neurons are located at presynaptic nerve terminals. These receptors have high calcium permeability and exhibit strong inward rectification, two important physiological features that enable them to facilitate transmitter release. Previously, we showed that intracellular polyamines act as gating molecules to block neuronal nAChRs in a voltage-dependent manner, leading to inward rectification. Our goal is to identify the structural determinants that underlie the block by intracellular polyamines and govern calcium permeability of neuronal nAChRs. We hypothesize that two ring-like collections of negatively charged amino acids (cytoplasmic and intermediate rings) near the intracellular mouth of the pore mediate the interaction with intracellular polyamines and also influence calcium permeability. Using site-directed mutagenesis and electrophysiology on alpha(4)beta(2) and alpha(3)beta(4) receptors expressed in Xenopus oocytes, we observed that removing the five negative charges of the cytoplasmic ring had little effect on either inward rectification or calcium permeability. However, partial removal of negative charges of the intermediate ring diminished the high-affinity, voltage-dependent interaction between intracellular polyamines and the receptor, abolishing inward rectification. In addition, these nonrectifying mutant receptors showed a drastic reduction in calcium permeability. Our results indicate that the negatively charged glutamic acid residues at the intermediate ring form both a high-affinity binding site for intracellular polyamines and a selectivity filter for inflowing calcium ions; that is, a common site links inward rectification and calcium permeability of neuronal nAChRs. Physiologically, this molecular mechanism provides insight into how presynaptic nAChRs act to influence transmitter release.
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10632582PMC6772427W1936443131What OpenQuestion holds
Registered trials
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