11. Tripartite synapse

What are astrocyte glutamate transporters

- glutamate taken up \= +ve charge into astrocyte
- uptake dependent on maintenance of transmembrane Na+ and K+ gradients
- 5 types of transporters

what is the tri-partite synapse

- astrocytes wrap around synapses and connect to both pre and post synaptic cells
- Neurotransmitter/gliotransmitter release
- results in elevated Ca2+ levels

Non-vesicular mechanisms of release

- occurs through Chloride channels, hemichannels or P2X7 receptors
- all allow passage of larger molecules
- When Ca2+ increase, it activates calcium sensitive proteins
- confirmation change, fusing of vesicle with cell membrane
- release of transmitters into extracellular space

Vesicular mechanisms of release

In neurones \= Ca2+ enters pres. terminal via voltage gated channels. rapid intracellular Ca2+ increase

In Glia \= Ca2+ comes from intracellular stores. Get slower but more sustained increase in Ca2+

Astrocyte glutamate receptors

- AMPA, Kinate ionotropic receptors
- Metabotropic glutamate receptors
- activation of receptors \= increase in Ca2+
- then get vesicular release depending on if its in neurones or glia

Intracellular Ca2+ storage

- majority stored in endoplasmic reticulum
- some in Cytosol
- some in extracellular
- separated by membranes

How is Ca2+ regulated

- Multiple ways for Ca2+ to come in
1. Ligand channel
2. voltage channel
3. glutamate channel
4. ATP Ca2+ pump

Ca2+ release from the ER

- waves \= NT binding to GPCR lead to increase in IP3 which caused and increase in Ca2+
- Positive feedback loop
- Ca2+ feeds on and effect is amplified

Technical considerations of experimental studies

- Other cells have GPCR, need to show what is happening specifically to/in astrocyte
- need to selectively stimulate astrocyte
- need to make sure enough dye is used

Study of Bergmann glia

- Study demonstrated that Ca2+ caused an increase in neuronal activity in astrocytes
- explain Ca2+ waves -- NT binding lead to Ca2+ activation

- black dye injected, Ca2+ sensitive
- stimulated along and activates synapse
- Big increase in Ca2+