L12 Neurotransmission

What are the two main types of neurotransmission?

Electrical (gap junctions) and chemical

Differences between electrical and chemical synapse

• distance between pre and post synaptic membrane

• type of transmission

• synaptic delay?

• uni or bidirectional?

Electrical: <5nm, by ion current, no, bidirectional 

Chemical: 20-40nm, by chemical neurotransmitter, yes 0.3-5ms, unidirectional

What structure enables direct electrical transmission?

Connexons (6 identical protein subunits forming gap junction channels).

Explain steps of chemical neurotransmission (5)

1. AP depolarizes the nerve terminal

2. VGCC opened

3. Calcium enter the nerve terminal increasing calcium conc inside

4. Neurotransmitters released by exocytosis

5. Neurotransmitters react with ligand gated channels in post synaptic cell membrane

What 3 proteins bind Ca²⁺ and their functions?

TCS

• Troponin – skeletal muscle contraction

• Calmodulin – smooth muscle contraction & gland secretion

• Synaptotagmin – triggers neurotransmitter release

How do voltage-gated Ca²⁺ channels differ from Na⁺ channels?

Ca²⁺ channels open more slowly but trigger cellular processes by binding to proteins.

What is the active zone?

What are docked vesicles?

What is meant by “quantal release”?

The presynaptic site where vesicles release neurotransmitter, rich in Ca²⁺ channels.

Vesicles positioned at the presynaptic membrane ready for release.

Neurotransmitter is released in discrete packets, each representing one vesicle’s contents

_{How are vesicles released step by step (6)}

1. Docking: Vesicles sit at the active zone.

2. Priming: v-SNAREs pair with t-SNAREs.

3. Trigger: Ca2+Ca^{2+}Ca2+ enters and binds synaptotagmin.

4. Action: Synaptotagmin drives SNARE “zippering.”

5. Fusion: Membranes merge → contents released.

6. Reset: NSF + ATP disassemble SNAREs for reuse.

What are the three vesicle release/recycling pathways?

KS

KR

E

• Kiss-and-stay: Vesicle releases contents and stays docked.

• Kiss-and-run: Vesicle detaches, refilled, and reused.

• Endocytosis via endosomes: Vesicle fully recycled.

What are the criteria that define a neurotransmitter? (5)

• Synthesized in presynaptic cell & stored in vesicles

• Released upon stimulation

• Specific receptor on postsynaptic cell

• Application mimics natural effect

• Blocking it inhibits normal function

What are the five major classes of neurotransmitters?

ACNPF

1. Simple amino acids – glutamate, glycine, GABA, aspartate

2. Classical – ACh, serotonin, dopamine, noradrenaline, adrenaline

3. Neuropeptides – insulin, glucagon, bradykinin, hypothalamic hormones

4. Purines/pyrimidines – ATP, adenine, guanine

5. Free radical gas – nitric oxide (NO)

Give examples of receptor types for ACh and noradrenaline.

• ACh → Nicotinic (N-cholinergic) or Muscarinic (M-cholinergic)

• NA/Adr → α and β adrenergic receptors

  • α = smooth muscle contraction

  • β = smooth muscle relaxation

What are ionotropic and metabotropic receptors, their speed and examples

Ligand gated ion channels, fast, eg nicotinic 

G protein coupled receptors, slow, modulatory eg adrenergic alpha and beta

Characteristics of a neuromuscular junction (5)

• has a motor end plate

• simple

• easily accessible

• large

• one muscle cell innervated by one axon

What are the possible fates of neurotransmitters after release? (3)

DER

How is Ach recycled? 

• Diffusion away from synaptic cleft

• Enzymatic degradation (e.g. AChE (acetylcholinesterase) breaks down ACh)

• Reuptake into presynaptic terminal via transporters for reuse or degradation

• AChE breaks it down into acetate + choline → choline reuptaken by chloine transporter on pre synaptic terminal and reused to synthesize new ACh using cohylnacetylesterase.

What causes Lambert-Eaton syndrome and how is it treated?

Antibodies against voltage-gated Ca²⁺ channels → reduced ACh release.

By decreasing ACh breakdown (pyridostigmine) or increasing Ca²⁺ influx (3,4-diaminopyridine).

What causes Myasthenia Gravis and how is it treated?

Antibodies against nicotinic ACh receptors → fewer functional receptors.

AChE inhibitors (pyridostigmine, neostigmine) to prolong ACh action.