vesicles

How are vesicles loaded with neurotransmitters?

Vesicular ATPase pumps protons to create a low pH gradient; specific transporters use this gradient to load neurotransmitters.

What is the role of vesicular ATPase?

Uses ATP to pump protons into vesicles, creating a low pH gradient (primary active transport).

Name four neurotransmitter-specific transporters

VGLUT (glutamate), VGAT (GABA/glycine), VAChT (acetylcholine), VMAT (monoamines).

What triggers neurotransmitter release?

An action potential depolarizing the presynaptic terminal.

How does an action potential lead to release?

Depolarizes the membrane, activating voltage-gated calcium channels (VGCCs).

What types of VGCCs are involved in release?

P/Q and N types.

At what voltage do VGCCs open?

-40 to -20 mV, only during action potentials.

What is the calcium equilibrium potential?

~ +60 mV, driving Ca²⁺ influx.

What are calcium nanodomains?

Small, high-concentration Ca²⁺ zones near VGCCs, enabling rapid neurotransmitter release

means that only a small amount of calcium is needed to entre the cell to trigger neurotransmitter release

What happens when Ca²⁺ enters the terminal?

Activates SNARE complex via synapotagmin, inducing vesicle fusion.

What are reserve vesicles?

Vesicles held by synapsin-actin links to the actin cytoskeleton, released by Ca²⁺ to replenish the active zone.

What is zippering in vesicle release?

Ca²⁺-synapotagmin interaction tightens SNARE complex, fusing vesicle with membrane.

What is partial zippering?

Loose SNARE interactions docking vesicles at the active zone.

What is full zippering?

Ca²⁺-induced tight SNARE interactions, priming vesicles for release.

What is the SNARE complex?

vSNARE (synaptobrevin) and tSNAREs (syntaxin, SNAP25) mediating vesicle fusion.

What is the quantal hypothesis?

Each vesicle releases one fixed packet (quanta) of neurotransmitter; total release is a multiple of quanta.

How fast is vesicle fusion?

Occurs in microseconds.

Summarize the exocytosis process

Action potential depolarizes terminal, opens VGCCs, Ca²⁺ influx activates SNARE complex, vesicle fuses, releases neurotransmitter.

What are the three mechanisms of vesicle recycling?

Clathrin-mediated endocytosis, reversible fusion pore (kiss and run/stay), and bulk endocytosis.

Describe clathrin-mediated endocytosis.

Vesicle fully fuses, clathrin forms coated pit, membrane bends inward, vesicle is cut and reformed; relatively slow.

Describe reversible fusion pore recycling.

Vesicle forms temporary pore; in kiss and run, it detaches to be refilled; in kiss and stay, it stays docked and is refilled; very fast.

When does bulk endocytosis occur?

After high-frequency stimulation; large membrane areas internalize and form endosomes to generate new vesicles; extremely fast.