L6 Chemicals in the Brain Flashcards
What does calcium activate?
Calcium calmodulin activated kinase II
What does Calcium calmodulin activated kinase II do?
phosphorylates synapsin
P-synapsin can no longer bind to the cytoskeleton, vesicles dock to the active zone
How are neurotransmitters released into the synaptic cleft via exocytosis
SNARE complexes form to pull membranes together
Ca2+ binds to synaptotagmin which forms a complex that binds SNARE complex and membrane
How does Botox prevent transmitter release?
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).
What are the 3 categories of NT?
amino acids
monoamines
neuropeptides
Give examples of NT that are a.a
Glu, GABA, Gly
Give examples of NT that are monoamines
Catecholamines (DA, NE, epinephrine)
5HT
Glutamate
How is it synthesized?
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
How does calcium cause release of NT into cleft?
Vesicles are docked onto plasma membrane
Ca2+ bound synaptotagmin causes membranes to fuse by binding SNAREs and plasma membrane
Docking
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
How is the vesicle membrane rapidly recovered (recycling)?
Endocytosis
How does Tetanus toxin prevent transmitter release?
inhibits the release of Glycine and GABA at inhibitory neuro
resulting in dis-inhibition of cholinergic neurons, which causes permanent muscle contraction
LEMS: Lambert-Eaton myasthenic syndrome is a type of muscle weakness. What is the mechanism by which it does this?
attacks presynaptic Ca2+ channels
Vesicular transporters
powered by proton gradient
ATPase proton pump loads up vesicles with H+
Plasma membrane transporters
powered by electrochemical gradient
[Na+] higher outside / [K+] higher inside
How are the neurotransmitters amino acids, monoamines and ACh stored and released?
- Synthesized locally in presynaptic terminal
- Stored in synaptic vesicles
- Released in response to local increase in Ca2+
How are neuropeptides synthesized and stored?
Synthesized in the cell soma and transported to the terminal
Stored in secretory granules
Released in response to global increase in Ca2+
Which types of neurotransmitters are fast?
amino acids
Which types of neurotransmitters are slow?
neuropeptides
GABA
Where is released?
Inhibitory
slightly hyperpolarises postsynaptic cell’s membrane
brain
Glycine
Where is it released?
Inhibitory
slightly hyperpolarises postsynaptic cell’s membrane
spinal cord and brainstem
What is the name of the enzyme that converts glutamate to GABA?
glutamic acid decarboxylase (GAD)
What happens during cerebral ischaemia?
reversal of the Na+ / K+ gradient
transporters release glutamate from cells by reverse operation
excitotoxic cell death (Ca2+ -> enzymes -> digestion)
How can GHB γ-hydroxybutyrate (date rape drug) lead to unconsciousness and coma?
Increases amount of GABA
Too much GABA can cause?
sedation/coma
Catecholamine synthesis
Tyrosine LDOPA DA NE Epinephrine
Where is NE synthesised?
Only NT to be synthesised within vesicles
Amphetamine
reverses transporter so pumps out transmitter and blocks reuptake (DA & NE)
Cocaine and Methylphenidate (Ritalin)
block DA reuptake into terminals
More DA in synaptic cleft – extended action on postsynaptic neuron
Selegiline
- MOA
- Treatment for what?
MAOi in dopaminergic nerve terminals
prevent degradation of DA
-treatment of early-stagePD,depression anddementia).
(Inhibitor prevents degradation of NT)
Entacapone
COMT inhibitor (treatment of PD)
5HT synthesis
Tryptophan
5-HTP
5HT
Serotonin storage, release and reuptake
- stored in vesicles
- signal terminated by reuptake by Serotonin transporters (SERTs) on presynaptic membrane
- destroyed by MAOs in the cytoplasm
MDMA (ecstasy)
causes NE and 5HT to run backwards releasing NT
Endocannabinoids
Small lipids which mostly cause reduced GABA release at certain inhibitory terminals
active component of Maurijana
