Neurotransmitters Flashcards
How does Clostridium Botulism prevent the pre-synaptic terminal from signalling the post-synaptic terminal?
Binds to nicotinic cholinergic receptors prevents the binding, docking and fusion of vesicles causing flaccid paralysis.
How does Clostridium tetanii cause uncontrolled muscle contraction?
Targets inhibitory Renshaw interneurons of the spinal cord
what type of receptor are nicotinic ACh receptors?
ionotropic, non-selective
What type of receptor are muscarinic receptors?
metabotropic
Name the agonists and antagonists for Nicotinic cholinergic receptors
Agonist: ACh, nicotine
Antagonist: curare
Name the agonists and antagonists of muscarinic ACh receptors.
Agonist: ACh, muscarine
Antagonists: atropine, ipratropium
What is the clinical application of curare?
muscle relaxant: used in capturing prey and seizures
Where do nicotinic ACh receptors occur?
Skeletal muscle: nAChRm
Neuronal (CNS, PNS): nAChn
Where do muscarinic ACh receptors occur?
M2 receptors: heart
M3 receptors: bronchioles, destrusor muscle, salivary gland, pancreatic duct, GI tract, occular SM
What is the action of M2 muscarinic receptors of the heart?
decrease HR
What are the overall actions of M3 muscarinic ACh receptors ?
Increased secretion of salivary glands, pancreatic duct, gastric acid
Increased contraction of bronchioles, GI tract and ocular smooth muscle
How do organophosphates affect ACh?
Prevents termination of ACh by acetycholinesterase –> refractory depolarised state
What would be the effects of reduced ACh termination?
refractory depolarised state –> muscle: muscle tremors, stiff gate, muscle spasms
parasympathetic and central synapses: salivataion (M3), lacrimation (M3), pupillary constriction (M3), diarrhea (M3), bradycardia (M2)
How does curare affect ACh binding to the post-synaptic terminal?
competitively binds to ACh receptors and blocks receptors that have already been activated by ACh
What is the consequence of preventing ACh signalling at the post-synaptic membrane?
relaxation of skeletal msucle
What is the function of myasthenia gravis?
ACh receptor degradation: exacerbates conditions where ACh competitive agonists are present as in the case of curare
What is atropine typically used for in veterinary medicine?
treats bradycardia, AV block and organophosphate poisoning (acetycholiesterase degradation)
How does atropine induce tachycardia?
Competitive binding of M2 muscarinic receptors of the heart prevent binding of ACh and consequentially reduce parasympathetic stimulation of HR and contractility.
What is the function of glutamate?
main stimulatory neurotransmitter of the CNS. Acts in opposition to GABA (inhibitor)
How is glutamate synthesised?
1) excitatory amino acid trasnporters (EAATs) –> glutamine (glial cells) –> system A transporter (SAT2) –> pre-synaptic terminal –> glutaminase –> glutamate –> vesicular glutamate transporters (VGLUT) –>
2) glucose –> transamination of a-ketoglutarate ((krebs cycle) –> glutamate
Name the Ionotropic glutamate receptors.
AMPA
NMDA
Kainate
Name which ions pass through the ionotropic glutamate receptor NMDA .
Ca influx
Na influx
K efflux
Name the general function of all glutamate ionotropic receptors.
excitatory stimulation (Na influx and K efflux)
What is the function of metabotropic glutamate receptors.
excitatory and inhibitory signals of post-synaptic vesicles
What is the action of ketamine?
Binds to NMDA ionotropic glutamate receptor at PCP binding site causing inhibition of the excitatory signals (Na, Ca)
What is the function of Mg2+ at the NMDA glutamate ionotropic receptor?
Mg2+ acts as to block transmission during resting membrane potential therefore receptors are only able to be activated during states of depolarisation.
What is long term potentiation?
With continual Ca influx, synaptic connections between neurons become stronger
mechanism underlying memory and learning
WHat are the consequences of excess glutamate?
Glutamate toxicity:
activation receptors –> destruction neurons –> stroke
What causes excess glutamate?
reduced enzymatic decomposition
increased glial cell uptake (EAAT) –> inflammation + further release glutamate
pathologic conditions with inappropriate activation of microglia and astrocytes –> relelase glutamate
What is the function of GABA (y-aminobutyric acid/glycine)?
Reduces anxiety, stress and fear