Cholinergic Neurotransmission

• Transmitter Synthesis and Degradation

  • Acetylcholine is synthesized from the immediate precursors acetyl coenzyme A and choline in a reaction catalyzed by choline acetyltransferase (choline acetylase).

A

Acetylcholinesterase

• Acetylcholinesterase

  • Rapid inactivation of acetylcholine is mediated by acetylcholinesterase.

  • Acetylcholinesterase is present at ganglia, visceral neuroeffector junctions, and neuromuscular junctional endplates.

  • Another type of cholinesterase, called pseudo-cholinesterase or butyrylcholinesterase has limited presence in neurons, but is present in glial cells. Most pseudocholinesterase activity is found in plasma and liver.

  • Pharmacological effects of anti-cholinesterase drugs are due to inhibition of acetylcholinesterase.

Acetylcholine Storage and Release

• Small random releases of acetylcholine-quanta, producing miniature end-plate potentials, are released by presynaptic terminals.

  • These small currents were linked to ACh release since anticholinesterases (neostigmine) increase their effects, while cholinergic receptor antagonist (tubocurarine, a nicotinic receptor blocker) blocks them.

• Anatomical counterpart to the electrophysiological quanta is the synaptic vesicle.

• The model is based on the nicotinic, skeletal neuromusclar junction.

• Synchronous exocytotic release of many more quanta, dependent on Ca²⁺ occur when an action potential reaches the terminal.

• Exocytotic release of acetylcholine and other neurotransmitters is inhibited by toxins elaborated by Clostridium botulinum

Category: Pharmacology Notes