examples of neurotransmitters
- dopamine
- serotonin
- acetylcholine
- GABA
are neurotransmitters proteins
- no!
- they are chemicals synthesised from amino acids
describe how a signal is transmitted from one neuron to another cell
1) the action potential travels down the axon to the axon terminal (the synapse)
2) voltage-sensitive Ca²⁺ channels open
3) Ca²⁺ rushes into the neuron down its concentration gradient.
4) Ca²⁺ causes neurotransmitter-containing vesicles to fuse with the plasma membrane and release their contents into the synaptic cleft (the tiny gap between neurons or neuron-muscle)
5) neurotransmitters diffuse across the cleft and bind to receptors on the post-synaptic cell
6) this chemical signal can then trigger a response in the post-synaptic cell (e.g., opening ion channels to start a new action potential, or causing muscle contraction)
describe how neurotransmitters lead to muscle contraction
1) voltage gated Ca2+ channels opens
2) the Ca2+ inflow causes ACh vesicle fusion and exocytosis
3) Ach binds ligand gated receptor/ion channel on muscle cell
4) Na+ flows in, K+ flows out
5) localised depolarisation causes opening of voltage gated Na+ channel
6) the propagating action potential reaches voltage-gated Ca2+ channels which signal the sarcoplasmic reticulum to release Ca2+ into the cytosol.
7) this Ca2+ releases causes muscle contraction
what is the dangerous toxin known to man
- botulism toxin
- the protein found in this toxin can inhibit muscle contraction
what’s botulism toxin used for in humans
botox!!!
describe how the botulism toxin works in our body
1) toxin binds specifically to motor neuron terminals (ACh-releasing neurons)
2) it enters the neuron via receptor-mediated endocytosis into an endosome
3) the toxin forms a pore in the endosome
4) its catalytic domain moves into the neuron cytoplasm
5) the toxin is a protease that cleaves v-SNARE proteins on synaptic vesicles
6) without the SNAREs, the vesicles can’t release ACh and muscle cannot contract
7) eventually the toxin is degraded and the cell can function normally (which is why botox is temporary)
how do neurotransmitters get loaded into vesicles
1) in the vesicles, there are V-class pumps that is pumping H+ ions against their concentration gradient into the vesicle
2) ther is an H+ antiporter that pumps H+ ions back out the vesicle (down their concentration gradient), and pumps in a neurotransmitter (against its concentration gradient)
examples of antiporters in neurotransmitter vesicles
- vGLUT
- vGABA
- vMAT
what happens after the vesicles have been packed with neurotransmitter
1) they travel to the periphery of the cell via kinesin motor proteins
2) they wait at the plasma membrane until the action potential arrives to be released
3) the action potential arrives
4) voltage-gated Ca2+ channels open to release Ca2+ into the cell
5) Ca2+ and synaptotagmin allow the vesicle to fuse with the plasma membrane and release the neurotransmitters
what happens to the neurotransmitters after they have been released into the synaptic cleft
1) symporters are used to recycle the neurotransmitters
2) an Na+/neurotransmitter symporter pumps both molecules back into the cell
what happens to the v-SNARES after they have fused with the plasma membrane
they are recycled via a clathrin/AP2 coat
what is a target of many drugs
the recycling symporters
example of a drug targeting dopamine recycling symporters
- cocaine/amphetamines/ritalin
- they bind to and competitively inhibit DAT (dopamine symporters)
- this prevents dopamine from clearing from the synaptic cleft
- this results in a significantly increased concentration of extracellular dopamine
- this dopamine continues to stay bound to the post-synaptic receptors and there is constant stimulation
example of a drug targeting serotonin recycling symporters
- antidepressants like fluoxetine and paroxetine, which are SSRIs, act on SERT (serotonin symporters)
- they bind to and competitively inhibit SERT, preventing it from clearing from the synaptic cleft
how long does the effect of SSRIs take
it can take weeks to notice behavioural changes
what do GABA transporters do
- GABA is inhibitory: it makes neurons less likely to fire
- GABA transporters remove GABA from the synapse and control how long and strong inhibition last
what do anti-anxiety drugs target
- enhance GABAergic inhibition in the brain
1) lorazepam binds to GABA-A receptors, which are ion channels that normally open when GABA binds
2) when GABA binds, the channel opens more easily or stays open longer, allowing more chloride ions (Cl⁻) into the neuron
3) more Cl⁻ enters = hyperpolarisation of the neuron
4) hyperpolarised neurons are less likely to fire, so overall brain activity is dampened
