Cholinergic Neurotransmission

The main targets for drug action are

Receptors

Enzymes

Transporters

Ion channels

General steps in neurotransmission

1. Choline (neuron) is taken into the cholinergic neuron (transmitter precursor) via carrier-mediated transport

2. Acetylcholine (transmitter) synthesised

3. Acetylcholine stored in vesicles (via carrier-mediated active transport)

4. Depolarization by action potential → Ca²⁺ influx

5. Acetylcholine released by Ca²⁺ mediated exocytosis (vesicle-SNARE proteins (synaptobrevin) & target SNARE proteins (syntaxin) form a complex

6. Acetylcholine binds to receptors (nicotinic/muscarinic) on the post-synaptic cell

7. Acetylcholine action is broken down by acetylcholinesterase into choline & acetate & is reuptaken

What is the rate-limiting step for acetylcholine production

Step 1: Neuron takes up transmitter precursor (choline uptake by cholinergic neuron)

How is Acetylcholine synthesised

Choline is acetylated using acetyl coenzyme A as a source of acetyl groups

This is catalysed by the synthetic enzyme, choline acetyltransferase

Name the 3 subtypes of nicotinic receptors

Muscle-type nicotinic

Ganglion-type nicotinic

CNS-type nicotinic

Name the 5 subtypes of muscarinic receptors

Muscarinic M1

Muscarinic M2

Muscarinic M3

Muscarinic M4

Muscarinic M5