NROSCI1017: Chap 24 NTs and ACh

Neurotransmitter

• Released into synaptic cleft

• Acts on nearby receptors

• Produces fast effects (ionotropic)

Neuromodulator

• Released into cleft or diffusely

• Produces slower, longer-lasting effects

• Often uses metabotropic receptors

What makes a neuromodulator slower than a neurotransmitter?

It often activates metabotropic receptors and diffuses more widely.

What are the basic criteria for calling something a neurotransmitter?

Present in vesicles, released by stimulation, mimics natural effect, has synthetic enzymes, has termination mechanisms, and predictable drug actions.

What factors affect NT synthesis?

Enzyme availability, precursor availability, and rate-limiting steps.

What are the main ways NT action is terminated?

Enzymatic breakdown, reuptake, diffusion, and receptor desensitization.

What determines the effect of a neurotransmitter?

The receptor type, not the neurotransmitter itself.

What are the four classes of neurotransmitters?

Classical NTs, amino acids, gaseous messengers, and neuropeptides.

Which NTs are found in small clear vesicles?

Classical NTs (e.g., ACh, monoamines) and amino acids.

Which molecules are in large dense-core vesicles?

Neuropeptides

What is released from small clear vesicles?

Fast-acting NTs at the active zone.

What is released from large dense-core vesicles?

Neuropeptides, usually extrasynaptically.

Where is ACh used in the PNS?

NMJ, all sympathetic preganglionic neurons, all parasympathetic pre- and postganglionic neurons.

Where is ACh used in the CNS?

Basal forebrain and reticular formation projections; mostly neuromodulatory.

What two substrates make ACh?

Choline + Acetyl-CoA.

What enzyme synthesizes ACh?

Choline Acetyltransferase (ChAT).

Why is ChAT important?

It’s the unique marker enzyme of cholinergic neurons.

What does the low-affinity choline transporter do?

Moves choline efficiently when levels are high.

What do High affinity choline uptake do?

High-affinity choline uptake using the Na⁺ gradient; main rate-limiting step for ACh production.

What transporter loads ACh into vesicles?

VAChT (Vesicular ACh Transporter).

What energy source does VAChT use?

Proton (H⁺) gradient.

How is choline uptake increased during high activity?

More HACU transporters are inserted during vesicle fusion.

How is choline uptake decreased?

HACU is removed through endocytosis during vesicle recycling.

How does precursor availability regulate ACh?

More choline → more ACh (mass action).

What enzyme breaks down ACh?

Acetylcholinesterase (AChE)

What are the products of ACh breakdown?

Choline + acetic acid

How fast is AChE?

Can break down about 5000 ACh molecules per second.

What is ACh’s role at the NMJ?

Primary neurotransmitter causing muscle contraction

What is ACh’s role in the sympathetic nervous system?

NT for all preganglionic neurons.

What is ACh’s role in the parasympathetic nervous system?

NT for both pre- and postganglionic neurons.

Where are cholinergic cell bodies located in the CNS?

Basal forebrain (nucleus basalis, medial septum) and reticular formation.