Neuroscience: excitotoxicity and neurotoxicity Flashcards
What is excitatory transmission?
increase electrical excitability on post-synaptic membrane - glutamate, ACh
What is inhibitory transmission?
decrease electrical excitability on post-synaptic membrane to prevent propagation of AP - glutamate
What is an inotropic receptor?
Membrane bound protein that responds to ligand binding by opening ion channel and allowing flow into a cell
Process of neurotransmission
neurotransmitter packaged into vesicles → presynaptic membrane depolarises due to AP → depolarisation causs Ca2+ channels an Ca2+ to flow into terminal → increase of intracellular Ca2+ triggers fusion of vesicles with presynaptic membrane → transmitter is released into extracellular space and diffuses across the cleft → some transmitters bind to postsynaptic membrane → receptors open
How are mitochondria damaged
Metabolic distress causes failure of ion homeostasis
This leads to increased intracellular Ca2+ and stimulates glutamate release
This activates post-synaptic receptors
CA2+ influx to cytoplasm and mitochondria
Apoptosis and cell death
Inhibitory neurotransmitter
GABA
Excitatory neurotransmitter
Glutamate
Is D1 inhibitory or excitatory?
Excitatory
Is D2 excitatory or inhibitory?
Inhibitory
Metabotropic receptor
indirectly linked with ion channels through signal transduction mechanisms e.g. G proteins - binds to receptor which releases a messenger and this is what causes ion influx
Differences between neuropeptides and neurotransmitters
Neurotransmitters are bigger, released slowly, last longer and can’t be re-uptaken
Examples of neuropeptides
ADH, cholecystokinin, endorphins, somatostatin, ACTH
Slow acting molecules
Dopamine, noradrenaline
Neurotransmitter in myasthenia graves and sx
ACh and droopy eyelids, tiredness, ptosis
What are neurotoxins?
- Destructive to nerve tissue
- Endogenous or exogenous
- E.g. heavy metals, botox, venoms, poisonous animals, ethanol
How is calcium removed from a cell when we are healthy?
- Glutamate binds to receptors
- Ca2+ enters from ER
- Na+ enters cell, allowing more Ca2+ to enter via exchangers
- Depolarisation - inhibits glutamate resorption
- Ca2+ stored in ER ad mitochondria and then actively pumped out of cell
How does excitotoxicity occur?
- Excessive glutamate binding
- Excessive calcium influx
- Cell can’t get rid of it quickly enough
- Ca2+ builds up in mitochondria
Consequences of excitotoxicity
High Ca2+ = glutamate release
Proteases and lipase activated by calcium
NO synthesised
Increased arachidonic release = more free radicals
Glial cells and excitotoxicity
Normally absorb glutamate
Failure = too much excitation
Glial cell destruction = Parkinson’s and Alzheimer’s
What is ischaemic brain injury?
no o2 means mitochondria dysfunction = Ca2+ build up
Organophosphate poisoning neurotransmitter and sx
ACh and bradycardia, SLUDGE
Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis
Neurotransmitter for Parkinson’s and sx
Dopamine - bradykinesia, Parkinson’s gait, resting tremor, rigidity
Neurotransmitter in benzodiazepine overdose and sx
GABA and drowsiness, blurred vision, unresponsive
Neurotransmitter in opioid overdose and sx
Opiates, bradypnoea, pinpoint pupils
Neurotransmitter in depression and sx
Serotonin and low mood and insomnia
Neurotransmitter in PKU and sx
Phenylalanine (precursor for dopamine etc), musty breath, seizures, fair skin and blue eyes
Examples of benzodiazepines
Diazepam, lorazepam
