Lesson 8: Acetylcholine & Cholinergic Synapses

Acetylcholine (ACh) Overview

  • ACh is the primary neurotransmitter in peripheral efferent (motor) neural pathways and plays roles in the CNS (sleep modulation, learning, memory).

Synthesis of Acetylcholine

  • Synthesis occurs in presynaptic nerve terminals.
  • Rate-limiting substrates: choline and acetyl-CoA.
  • Choline acetyltransferase (ChAT) catalyzes ACh formation from acetyl-CoA and choline.

Cholinergic Receptors

  • Two types:
    • Nicotinic ACh Receptors (nAChR):
    • Ionotropic, nonselective cation channels.
    • Found in neuromuscular junction, autonomic ganglia, CNS.
    • Muscarinic ACh Receptors (mAChR):
    • Metabotropic, found in CNS, heart, smooth muscle, GI tract.
    • Five types identified (M1 to M5).

Acetylcholine Release and Elimination

  1. Action potential increases intracellular Ca^{2+} leading to vesicle fusion and ACh release.
  2. ACh binds to postsynaptic receptors and is hydrolyzed by acetylcholinesterase (AChE) into acetate and choline.
  3. Choline is recycled for ACh synthesis.

Receptor Signal Transduction

  • nAChR (Autonomic ganglia & NMJ):
    • Influx of Na^{+} causing depolarization and contraction.
  • mAChR:
    • Coupling of odd-numbered receptors (M1, M3, M5) to Gq, leading to increased Ca^{2+}.
    • Coupling of even-numbered receptors (M2, M4) to Gi, leading to decreased cAMP and hyperpolarization.

Key Functions

  • ACh roles in various systems:
    • Neuromuscular junction: muscle contraction.
    • CNS: multiple effects including arousal and attention.