T1L6 chemicals in the brain

Question 1

vesicular release

Answer 1

• action potential causes Ca2+ to flow into cell
• Ca2+ activates CaMKII (phosphorylates synapsin)
• this releases vesicle from cytoskeleton
• SNARE complex binds the vesicle to the membrane of the active site using synaptotagmin
• vesicle then recovered by endocytosis, is refilled and reused

Question 2

synapsin

Answer 2

holds vesicle to cytoskeleton. phosphorylated by CaMKII

Question 3

CaMKII

Answer 3

calcium calmodulin activated kinase II

- phosphoyates synasin

Question 4

SNARE

Answer 4

fuses vesicle to membrane of active site

- synaptotagmin

Question 5

clostridal toxins

Answer 5

eg tetanus toxin, botox

• cleavage of snare complex
• no exocytosis so no neurotransmitter release

Question 6

tetanus toxin

Answer 6

• inhibits release of glycine and GABA at inhibitory neurons, resulting in disinhibition of cholinergic neurons – so permenantly contracting muscle

Question 7

botox

Answer 7

• acts on neuromuscular junction. muscle becomes permanently relaxed
• botulinum toxin

Question 8

4 categories of neurotransmitter

Answer 8

amino acids
monoamines
acetylcholine
( synthesized in presynaptic terminal, stored in synaptic vesicles, released in response to LOCAL ca2+)
- fast

neuropeptides
(synthesized in the cell soma and transported to the terminal, stored in secretory granules, released in response to GLOBAL ca2+)
- slow

Question 9

low frequency impulses

Answer 9

activate fast transmitters eg glutamate

• local ca2+ increase

don’t activate slow transmitters eg neuropeptide

Question 10

high frequency impulses

Answer 10

activate both types of neurotransmitter

• global ca2+ increase

Question 11

amino acid transmitters

Answer 11

1) excitatory
- slightly depolarises postsynaptic cells membrane
- glutamate (Glu)

2) inhibitory
- slightly hyperpolarises the postsynaptic cells membrane
- GABA (brain)
- glycine (gly)

Question 12

diffuse modulatory systems

Answer 12

• eg serotonergic system

function in:

• mood
• sleep
• pain
• emotion
• appetite

Question 13

glutamate (glu)

Answer 13

• synthesized in presynaptic terminal from kerbs cycle and from glutamine converted by glutaminase to glutamate
• loaded and stored in vesicular glutamate transporters
• reuptake by excitatory amino acid transporters (EAATS)
• EXCITATION

Question 14

GABA

Answer 14

• synthesized from glutamate in a reaction catalysed by glutamic acid decarboxylase (GAD)
• cleared from synapse by reuptake using transporters

Question 15

regulation of amino acid neurotransmitter release

Answer 15

too much Glu/ too little GABA&raquo_space; hyperexcitability and epilepsy exotoxicity

cerebral ischaemia:
- metabolic events that maintain electrochemical balance are destroyed

• reverse NA/K gradient
• transporters release glutamate by reverse operation
• cell death

Question 16

GHB

Answer 16

• date rape
• GABA metabolite that can be converted back to gaba
• unconsciousness and coma

Question 17

MONOAMINES 2 categories

Answer 17

catecholamines:

• (dopamine, adrenaline, noradrenaline)
• loaded into vesicles by vesicular monoamine transporters (VMATs)
• released by ca2+ dependant exocytosis

idolamines:

• (serotonin)
• stored in vesicles

Question 18

catecholamine synthesis - dopamine and adrenaline

Answer 18

pic slide 28

Question 19

idolamine synthesis - serotonin

Answer 19

pic slide 33

Question 20

ACETYLCHOLINE

Answer 20

eg acetylcholine

• choline acetyltransferase converts choline + acetylcoa to acetylcholine
• choline transported back into presynaptic terminal after release; converted bac into acetylcholine
• amount of choline is rate limiting step

Question 21

NEUROPEPTIDES

Answer 21

• synthesized in cell soma and transported to terminal
• stored in secretory granules
• released in response to GLOBAL ^Ca2+
• they are short polypeptide chains 3 to 36 aa
• over 100 described
• slow transmission
• released following the secretory pathway– different to small molecules
• vesicle membrane recycled but not reused
• signal terminated by neuropeptides diffusing away from synapse and degredation by proteases
• effect is longer duration

Question 22

neuropeptide vs small molecule synapse comparison

Answer 22

pic s41

Question 23

soluble gases as neurotransmitters

Answer 23

eg no/co

• no made in postsynaptic neuron by nitric oxide synthase
• not stored and rapidly diffuses
• diffuses between cells
• converted to inactive compound
• useful for coordinating multiple cells in small region

Question 24

endocannabinoids

Answer 24

• small lipids

- reduce gaba at inhibitory terminals