Lesson 11: Acetylcholine

Acetylcholine Overview

  • Primary neurotransmitter in the parasympathetic nervous system.
  • Stimulates cholinergic receptors (Nicotinic & Muscarinic).

Cholinergic Receptors

Types

  • Nicotinic: Ion channels, subtypes include:

    • Type N (NN): ganglionic, neuronal CNS
    • Type M (NM): neuromuscular junction, SNS ganglia

  • Muscarinic: G-protein linked, subtypes include:

    • M1: CNS
    • M2: postganglionic effector organs
    • M3, M5: various target cells

Signal Transduction

  • Nicotinic: fast synaptic transmission via ion channels.
  • Muscarinic: slow responses via G-protein activation (e.g., phospholipase C activation or adenylate cyclase inhibition).

Acetylcholine Synthesis

  1. Synthesis occurs at presynaptic nerve terminal.
  2. Rate-limiting factors: choline and acetyl-CoA availability.
  3. Steps:
    • Acetyl-CoA produced in mitochondria and released into cytoplasm.
    • Choline transported from blood into nerve terminal cytoplasm.
    • Choline and Acetyl-CoA combined by choline acetyltransferase (ChAT) to produce ACh.
    • Packaged into vesicles.

Acetylcholine Release

  1. Action potential depolarizes the nerve terminal.
  2. Voltage-gated Ca2+ channels open, allowing Ca2+ influx.
  3. Ca2+ facilitates ACh vesicle fusion with nerve terminal, leading to ACh release via exocytosis.
  4. Mg2+ can inhibit Ca2+ action, leading to muscle weakness.

Acetylcholine Metabolism

  1. Acetylcholinesterase (AChE) hydrolyzes ACh after it binds to receptors.
  2. Byproducts: choline and acetate.
  3. Choline reabsorbed into the nerve terminal for further ACh synthesis; acetate diffuses away.

Key Notes

  • ACh is not reused; must be metabolized for precise organ control.
  • AChE is essential for rapid breakdown of ACh after neurotransmission.