Neurobiology of Acetylcholine: Synthesis, Release, Receptors, and Pharmacology

Vocabulary flashcards defining key neurotransmitters, enzymes, transporter proteins, receptors, toxins, and pharmacological compounds associated with the cholinergic system based on the lecture material.

Choline acetyltransferase (ChAT)

An enzyme present in the cytoplasm of cholinergic neurons that catalyzes the single-step synthesis of acetylcholine by transferring an acetyl group ($-\text{COCH}_3$) from acetyl CoA to choline.

Vesicular ACh transporter (VAChT)

A transport protein in the synaptic vesicle membrane that loads acetylcholine molecules into vesicles for storage and subsequent release.

Vesamicol

A drug that selectively blocks the vesicular ACh transporter (VAChT), resulting in decreased vesicular ACh, increased cytoplasmic ACh levels, and reduced transmitter release upon cell activation.

Black widow spider venom

Venom from Latrodectus mactans containing a toxin that triggers a massive release of acetylcholine at peripheral synapses, causing muscle pain, tremors, nausea, and sweating.

Botulinum toxin

An extremely potent toxin produced by Clostridium botulinum that inhibits acetylcholine release at nerve terminals by preventing synaptic vesicle fusion with the presynaptic membrane, leading to muscular paralysis.

Botox

The trade name for purified botulinum toxin A, used cosmetically to reduce dynamic facial wrinkles by injecting it locally to paralyze specific facial muscles through ACh release blockade.

Acetylcholinesterase (AChE)

An enzyme responsible for breaking down acetylcholine in the synaptic cleft or neuromuscular junction into choline and acetic acid.

G4 AChE

A tetrameric form of acetylcholinesterase containing four globular subunits, the majority of which are linked to a membrane anchor to break down ACh rapidly after its release.

A12 AChE

An asymmetric form of acetylcholinesterase containing 12 subunits and a collagen tail, secreted by muscle cells at the neuromuscular junction and anchored to the extracellular matrix.

Hemicholinium-3 (HC-3)

A drug that blocks the presynaptic membrane choline transporter, preventing choline reuptake and causing a decline in the rate of acetylcholine production.

Donepezil

A synthetic, reversible central and peripheral acetylcholinesterase inhibitor (trade name Aricept) used to enhance ACh availability for modest cognitive benefit in Alzheimer's disease.

Physostigmine

A naturally occurring reversible acetylcholinesterase inhibitor isolated from Calabar beans that readily crosses the blood–brain barrier; also used topically to treat glaucoma.

Organophosphorus compounds

Chemical agents that produce nearly irreversible inhibition of acetylcholinesterase by forming covalent bonds or dissociating extremely slowly from the enzyme; used as insecticides and chemical nerve gases.

Sarin

A synthetic organophosphorus chemical warfare agent that causes irreversible AChE inhibition, leading to profuse sweating, convulsions, and asphyxiation due to diaphragm muscle paralysis.

Pyridostigmine

A synthetic reversible acetylcholinesterase inhibitor that does not cross the blood–brain barrier, used to treat myasthenia gravis and administered as a protective antidote prior to nerve gas exposure.

Myasthenia gravis

An autoimmune neuromuscular disorder characterized by antibodies attacking and blocking skeletal muscle cholinergic receptors, causing generalized muscle weakness, severe fatigue, and ptosis.

Basal forebrain cholinergic system (BFCS)

A diffuse group of cholinergic neurons (including the nucleus basalis, substantia innominata, medial septal nucleus, and diagonal band nuclei) providing dense innervation to the cerebral cortex, hippocampus, and limbic structures.

Nicotinic acetylcholine receptors (nAChRs)

Ionotropic cholinergic receptors composed of five protein subunits forming a central channel that allows $\text{Na}^+$ and $\text{Ca}^{2+}$ influx upon agonist binding, mediating fast excitatory responses.

Depolarization block

A state caused by continuous nicotinic receptor stimulation wherein the membrane resting potential is lost, rendering the cell unexcitable until the agonist is removed and the membrane repolarizes.

Succinylcholine

A muscle nicotinic receptor agonist resistant to AChE breakdown that produces persistent depolarization block, used medically to induce brief paralysis for medical procedures.

Mecamylamine

An antagonist at neuronal nicotinic receptors that blocks nAChRs both centrally in the brain and peripherally in autonomic ganglia.

d-Tubocurarine

A selective muscle nicotinic receptor antagonist isolated from curare that causes muscular paralysis and exhibits low penetrance across the blood–brain barrier.

Neonicotinoids

A class of synthetic receptor agonists (such as imidacloprid) that selectively target insect nicotinic receptors to produce continuous lethal neuronal excitation; widely used as agricultural insecticides.

Muscarinic acetylcholine receptors

A family of five metabotropic receptor subtypes ($\text{M}_1$ through $\text{M}_5$) that signal through second-messenger systems to mediate excitatory or inhibitory cholinergic effects.

Parasympathomimetic agents

Muscarinic receptor agonists (e.g., muscarine, pilocarpine, and arecoline) that mimic the physiological actions of parasympathetic nervous system activation.

Parasympatholytic agents

Muscarinic receptor antagonists (e.g., atropine and scopolamine) that block parasympathetic nervous system functions.

Atropine

A naturally occurring muscarinic antagonist isolated from Atropa belladonna used medically for pupillary dilation during eye examinations and to decrease body secretions before surgery.

Scopolamine

A muscarinic receptor antagonist that crosses the blood–brain barrier to produce central effects such as drowsiness, euphoria, amnesia, and dreamless sleep.

Xerostomia

The clinical condition of dry mouth, caused by reduced salivation due to the blockade of peripheral muscarinic receptors associated with salivary glands.