CHOLINERGIC TRANSMISSION

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).



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 glia. 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 release of acetylcholine-quanta, producing miniature end-plate potentials (mepps) , are released by presynaptic terminals.
These small currents were linked to ACh release since anticholinesterases (neostigmine) increased their effects, while cholinergic receptor antagonist (tubocurarine, a nicotinic receptor blocker) blocked.
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.
Botulism

Botulism is caused by the most potent neurotoxins known. The neurotoxins are produced and liberated by Clostridium botulinum.
C. botulinum, ubiquitously found in soil and marine environments, is a group of gram positive anerobes that form spores.

Eight distinct toxins have been characterized, all but one being neurotoxic.
Botulinum neurotoxin affects cholinergic nerve terminals:
postganglionic parasympathetic endings
neuromuscular junctions
peripheral ganglia
CNS is not involved.
Botulinum neurotoxin prevents acetylcholine release:
binds presynaptically
internalized in vesicular form
released into the cytoplasm
the toxin(s), (zinc endopeptidases) causes proteolysis of components of the neuroexocytosis system.