Neurosurgery notes/Anatomy/Peripheral nerves anatomy/Channels/Acetylcholine

Acetylcholine

View Details
Status
Done
logo
Parent item
Channels

Acetylcholine

  • Synthesis
    • In nerve terminals
    • From precursors acetyl coenzyme A (acetyl CoA, which is synthesized from glucose) + choline →
      • Choline is present in plasma at a high concentration (about 10 mM) and is taken up into cholinergic neurons by a high-affinity Na+/choline transporter.
    • Catalyzed by choline acetyltransferase (CAT).
    • After synthesis in the cytoplasm of the neuron, a vesicular ACh transporter loads approximately 10,000 molecules of ACh into each cholinergic vesicle.
  • Breakdown
    • Acetylcholinesterase (AChE) hydrolysis Ach → acetate + choline.
    • The choline produced by ACh hydrolysis is transported back into nerve terminals and used to resynthesize ACh.

Receptor

  • Nonselective cation channels
Nicotinic receptors
Muscarinic receptors
Located
• Neuromuscular junction N1
• Preganglionic endings of both sympa­thetic and parasympathetic fibers N2
• All postganglionic parasympathetic endings
• Postganglionic sympathetic endings of sweat glands
• Muscarinic ACh receptors are highly expressed in the striatum and various other forebrain regions, where they exert an inhibitory influence on dopamine-mediated motor effects
Subtypes
N1, N2
M1, M2, M3, M4, M5
Effects
All excitatory
M1, M2, M5 Excitatory
M3, M4 inhibitory
Ligand gated
Ion channels open upon activation
Metabotropic G protein coupled receptors
Response
Fast
Slow
Ligand
Acetylcholine, Nicotine, α-bungarotoxin
Acetylcholine, muscarine
A diagram of a cell membrane AI-generated content may be incorrect.
Acetylcholine receptor and modulators. (Reprinted with permission from Greenstein and Greenstein, p.101.²²)

Pathology

A diagram of a cell membrane AI-generated content may be incorrect.

Botulinum toxin

  • Irreversibly blocks release of acetylcholine (ACh) from presynaptic nerve terminal.

Tetraethylammonium (TEA)

  • A quaternary ammonium cation with the chemical formula [Et4N]+
  • Effects
    • A competitive inhibitor at nicotinic acetylcholine receptors
    • Block voltage-dependent K+ channels in nerve
  • Symptoms:
    • Curariform like symptoms
    • Tremors, incoordination, flaccid prostration, and death from respiratory failure within 10–30 minute
notion image
 

Conotoxins:

  • From venom of the marine cone snail
      • Type
      inhibits
      α-conotoxin
      Nicotinic acetylcholine receptors at nerves and muscles,
      δ-conotoxin
      Voltage-dependent sodium channels,
      κ-conotoxin
      Potassium channels,
      μ-conotoxin
      Voltage-dependent sodium channels in muscles,
      ω-conotoxin
      N-type voltage-dependent calcium channels.
Zoologger: The snail that's bust a gut to become toxic | New Scientist

Chlorotoxin

  • Found in the venom of deathstalker scorpion
  • Acts as a Cl− channel blocker.
    • Studies being done for visualisation and treatment of Glioma as Gliomas have high amounts of Cl channel
Deathstalker' Scorpion's Rapid Strike Caught on Film | Live Science

α-bungarotoxin

  • Can produce postsynaptic effects similar to that observed with curare, by binding specifically to the subunits of the nicotinic ACh receptor.
  • Found in the venom of snakes and kraits
  • Can result in severe symptoms including bleeding or hemorrhage, paralysis and tissue damage that can result in amputation.
Common krait - Wikipedia
 

Curare

  • competitively antagonises binding of ACh to the postsynaptic nicotinic receptor.