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Related Concept Videos

Cholinergic Receptors: Nicotinic01:15

Cholinergic Receptors: Nicotinic

Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
Cholinergic Receptors: Muscarinic01:25

Cholinergic Receptors: Muscarinic

The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine. 
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Direct-Acting Cholinergic Agonists: Pharmacological Actions00:59

Direct-Acting Cholinergic Agonists: Pharmacological Actions

Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...

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Updated: May 18, 2026

Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells
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Positive modulation of the α9α10 nicotinic cholinergic receptor by ascorbic acid.

J C Boffi1, C Wedemeyer, M Lipovsek

  • 1Instituto de Investigaciones en Ingeniería, Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Buenos Aires, Argentina.

British Journal of Pharmacology
|September 22, 2012
PubMed
Summary

Ascorbic acid potentiates α9α10 nicotinic cholinergic receptors (nAChRs), offering potential therapeutic benefits for inner ear disorders by enhancing receptor function. This study identifies a novel positive modulator for these crucial auditory pathway receptors.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Ototoxicology

Background:

  • The α9α10 nicotinic cholinergic receptors (nAChRs) are critical for protecting against acoustic trauma.
  • Pharmacological potentiation of these receptors presents a therapeutic strategy for hearing disorders.

Purpose of the Study:

  • To characterize ascorbic acid as a positive allosteric modulator of recombinant α9α10 nAChRs.
  • To explore the therapeutic potential of ascorbic acid in modulating auditory receptor function.

Main Methods:

  • Two-electrode voltage-clamp recordings were performed in Xenopus laevis oocytes expressing α9α10 nAChRs.
  • Acetylcholine (ACh)-evoked responses were analyzed in the presence of varying concentrations of ascorbic acid.

Main Results:

  • Ascorbic acid demonstrated concentration-dependent potentiation of ACh responses in α9α10 nAChRs (1-30 mM).
  • The potentiation significantly enhanced maximal evoked currents (240 ± 20%) without altering the current-voltage profile or ACh affinity.
  • The effect was specific to L-ascorbic acid and suggested a positive allosteric mechanism, not an antioxidant effect.

Conclusions:

  • Ascorbic acid acts as a positive modulator of α9α10 nAChRs, representing a novel therapeutic agent.
  • This finding opens new avenues for drug design targeting inner ear disorders by modulating nAChR activity.