L6 Chemicals in the Brain

Question 1

What does calcium activate?

Answer 1

Calcium calmodulin activated kinase II

Question 2

What does Calcium calmodulin activated kinase II do?

Answer 2

phosphorylates synapsin

P-synapsin can no longer bind to the cytoskeleton, vesicles dock to the active zone

Question 3

How are neurotransmitters released into the synaptic cleft via exocytosis

Answer 3

SNARE complexes form to pull membranes together

Ca2+ binds to synaptotagmin which forms a complex that binds SNARE complex and membrane

Question 4

How does Botox prevent transmitter release?

Answer 4

decreases neuromuscular transmission of ACh

acts directly at the neuromuscular junction.

The muscles lose all input and so become permanently relaxed (treatment of muscle spasms).

Question 5

What are the 3 categories of NT?

Answer 5

amino acids
monoamines
neuropeptides

Question 6

Give examples of NT that are a.a

Answer 6

Glu, GABA, Gly

Question 7

Give examples of NT that are monoamines

Answer 7

Catecholamines (DA, NE, epinephrine)

5HT

Question 8

Glutamate

How is it synthesized?

Answer 8

Excitatory –
slightly depolarises the postsynaptic cell’s membrane

CNS
Synthesis:
1) from glucose via the Krebs cycle
2) from glutamine converted by glutaminase into Glutamate

stored in vesicles VGLUTS

Question 9

How does calcium cause release of NT into cleft?

Answer 9

Vesicles are docked onto plasma membrane

Ca2+ bound synaptotagmin causes membranes to fuse by binding SNAREs and plasma membrane

Question 10

Docking

Answer 10

Docking then priming – Vesicles wait for the signal then fuse with target membrane then fusion:

• Vesicles carry v-SNAREs – Synaptobrevin and Synaptotagmin
• Active zones in plasma membrane carry t-SNAREs – syntaxin-1 and SNAP-25
• SNARE protein held in place by complexin – stops fusion of membrane
• Ca2+ binds to synaptotagmin
• displaces complexin
• membrane fusion
• NT released
• Extra Ca2+ is removed from cytosol by Ca2+ ases (pumps) as excess can kill the cell
• Endocytosis – vesicle is re-filled or broken down

Question 11

How is the vesicle membrane rapidly recovered (recycling)?

Answer 11

Endocytosis

Question 12

How does Tetanus toxin prevent transmitter release?

Answer 12

inhibits the release of Glycine and GABA at inhibitory neuro

resulting in dis-inhibition of cholinergic neurons, which causes permanent muscle contraction

Question 13

LEMS: Lambert-Eaton myasthenic syndrome is a type of muscle weakness. What is the mechanism by which it does this?

Answer 13

attacks presynaptic Ca2+ channels

Question 14

Vesicular transporters

Answer 14

powered by proton gradient

ATPase proton pump loads up vesicles with H+

Question 15

Plasma membrane transporters

Answer 15

powered by electrochemical gradient

[Na+] higher outside / [K+] higher inside

Question 16

How are the neurotransmitters amino acids, monoamines and ACh stored and released?

Answer 16

• Synthesized locally in presynaptic terminal
• Stored in synaptic vesicles
• Released in response to local increase in Ca2+

Question 17

How are neuropeptides synthesized and stored?

Answer 17

Synthesized in the cell soma and transported to the terminal

Stored in secretory granules

Released in response to global increase in Ca2+

Question 18

Which types of neurotransmitters are fast?

Answer 18

amino acids

Question 19

Which types of neurotransmitters are slow?

Answer 19

neuropeptides

Question 20

GABA

Where is released?

Answer 20

Inhibitory
slightly hyperpolarises postsynaptic cell’s membrane

brain

Question 21

Glycine

Where is it released?

Answer 21

Inhibitory
slightly hyperpolarises postsynaptic cell’s membrane

spinal cord and brainstem

Question 22

What is the name of the enzyme that converts glutamate to GABA?

Answer 22

glutamic acid decarboxylase (GAD)

Question 23

What happens during cerebral ischaemia?

Answer 23

reversal of the Na+ / K+ gradient

transporters release glutamate from cells by reverse operation

excitotoxic cell death (Ca2+ -> enzymes -> digestion)

Question 24

How can GHB γ-hydroxybutyrate (date rape drug) lead to unconsciousness and coma?

Answer 24

Increases amount of GABA

Question 25

Too much GABA can cause?

Answer 25

sedation/coma

Question 26

Catecholamine synthesis

Answer 26

Tyrosine
LDOPA
DA
NE 
Epinephrine

Question 27

Where is NE synthesised?

Answer 27

Only NT to be synthesised within vesicles

Question 28

Amphetamine

Answer 28

reverses transporter so pumps out transmitter and blocks reuptake (DA & NE)

Question 29

Cocaine and Methylphenidate (Ritalin)

Answer 29

block DA reuptake into terminals

More DA in synaptic cleft – extended action on postsynaptic neuron

Question 30

Selegiline

• MOA
• Treatment for what?

Answer 30

MAOi in dopaminergic nerve terminals
prevent degradation of DA

-treatment of early-stagePD,depression anddementia).

(Inhibitor prevents degradation of NT)

Question 31

Entacapone

Answer 31

COMT inhibitor (treatment of PD)

Question 32

5HT synthesis

Answer 32

Tryptophan
5-HTP
5HT

Question 33

Serotonin storage, release and reuptake

Answer 33

• stored in vesicles
• signal terminated by reuptake by Serotonin transporters (SERTs) on presynaptic membrane
• destroyed by MAOs in the cytoplasm

Question 34

MDMA (ecstasy)

Answer 34

causes NE and 5HT to run backwards releasing NT

Question 35

Endocannabinoids

Answer 35

Small lipids which mostly cause reduced GABA release at certain inhibitory terminals

active component of Maurijana