The Nervous System Flashcards
How do you tell the difference between a sympathetic and a parasympathetic nerve?
Preganglionic neuron for a parasympathetic nerve is much longer than the preganglionic neuron for a sympathetic nerve
What neurotransmitter is released at preganglionic synapse for parasympathetic nerves?
+sympathetic nerves?
Acetylcholine for both
What neurontransmitter is released at the terminal synapse for a sympathetic nerve?
+parasympathetic nerve?
Sympathetic- Noradrenaline
Parasympathetic- Acetylcholine
Where do nerves for the sympathetic nervous system emanate from?
Thoracolumbar region of the spinal cord
Where do nerves for the parasympathetic nervous system emanate from?
Cranio and sacral regions of the spinal cord
How is neurotransmitter released from a terminal junction?
simple explanation
Action potential travels down the axon of the presynaptic nerve where it reaches the terminal region. Depolarisation of terminal region causes voltage dependant Ca2+ channels to open, allowing an influx of Ca2+ which causes vesicles containing neurotransmitter in the terminal region to fuse with the presynaptic membrane and release the neurotransmitter.
What is presynaptic autoinhibitory agonism?
When the neurotransmitter which was released from the presynapse, comes back to the presynaptic membrane and causes inhibition of further neurotransmitter release.
How are neurotransmitter synthesised and stored within the presynapse?
A precursor to the neurotransmitter enters the cell, normally through active uptake. Enzyme cascade occurs which turns the precursor to the neurotransmitter. The NT end up in vesicles where they’re stored to protect them from enzymes in the cytoplasm and to increase to concentration of the NT.
What can inhibit/stimulate precursor uptake of a presynaptic cell?
Hemicholinium inhibits precursor uptake.
An excess of the precursor will increase precursor uptake.
What can inhibit precursor turning into enzyme within presynaptic cell?
AMPT inhibits the enzymes of the enzyme cascade
What can inhibit neurotransmitter release of a presynaptic cell?
Reserpine cases leakage of the NT which ultimately inhibits NT release
What is the precursor to Dopamine?
L-DOPA
How is the depolarisation of the terminal end inhibited?
Guanethidine is a drug which inhibits terminal region depolarisation of presynaptic cells that release noradrenaline.
How is Ca2+ influx into presynaptic cell inhibited?
Conotoxin drug
What is a ‘dirty drug’?
A drug which has multiple receptors in the body it can bind to so its effect within the organism can be wide.
What does chlonidine do?
Works to inhibit α2 adrenoceptor so can inhibit presynaptic autoinhibitory agonism.
Makes noradrenaline effect last longer as the NT can not be taken up by the presynpase.
How is the neurotransmitter terminates?
Diffusion (not important considering geometry of synapse)
Enzymes degrade NT to metabolites
Reuptake of NT via presynaptic membrane
What drugs can inhibit uptake of neurotransmitter
Chlondine works to inhibit α2 adrenoceptor
Cocaine inhibits NA reuptake
Fluoxetine (prozac) inhibits serotonin and NA reuptake
What does neostigmine do?
Inhibits the AChE by carbamylation of the esteratic site of AChE to provide a medium duration inhibition of AChE
What does salbutamol do and act on?
It treats asthma
It acts on β2 receptors that are stimulated by noradrenaline.
What does phenylephrine do and act on?
It is decongestant
It acts on α1 receptors that are stimulated by noradrenaline.
What does bromocrotptine do and act on?
It treats Parkinson’s Disease
It acts on D2 receptors that are stimulated by dopamine.
What does morphine do and act on?
It relieves pain
It acts on μ receptors that are stimulated by Enkephalin.
What does diazepam do and act on?
It treats anxiety
It acts on A receptors that are stimulated by GABA.
What does prazosin do and act on?
It reduces blood pressure.
It acts as an antagonist on α1 receptors that are stimulated by noradrenaline.
What does propranolol act on and what is its clinical use?
It is used to treat abnormal cardiac rhythm, myocardial infarction and angina (reduced bloodflow to cardiac muscle) –>(reduces blood pressure overall)
It acts as an antagonist on β2 and β1 receptors.
What does atracurium do and act on?
It is a muscle relaxant.
It acts as an antagonist on nicotinic receptors that are stimulated by ACh.
What does atropine do and act on?
It blocks secretions (like saliva), brings about mild tachycardia and dilate pupil.
It acts as an antagonist on muscarinic receptors.
What does trifluoperazine do and act on?
It is an antipsychotic drug.
It acts as an antagonist on D” receptors that are stimulated by Dopamine.
What does Botulinum Toxin do and act on?
It stops ACh release.
It inhibits NT vesicle fusion to membrane.
What does Sildenafil do?
It inhibits the breakdown of the second messenger substance cyclic GMP produced by nitric oxide in erectile tissue.
What is a putative neurotransmitter?
It ‘might’ be a neurotransmitter in comparison to an established neurotransmitter.
What are the steps of establishing a neurotransmitter?
- Identification of biological activity
- Identification of active principle
- See if the neurotransmitter satisfy criteria for a neurotransmitter
- Identification of physiological roles
What is the motor unit?
The motor nerve plus the muscle fibres which it controls.
How big is the gap between the nerve and the muscle in a NMJ?
60 nm
How is ACh synthesised?
Choline is the precursor to ACh.
Choline in addition to acetylcoenzyme (AcCoA) by the action of Choline Acetyl Transferase (CAT).
What is the structure of ACh?
https://sites.google.com/a/macalester.edu/nerve-agents/_/rsrc/1467895574698/home/acetylcholine-and-vx/Capture%208.JPG?height=148&width=320
What is the structure of Choline?
https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=305&t=l
What do hemicholiniums do?
Inhibit synthesis of ACh by blocking uptake/reuptake of choline at presynapse.
What drug inhibits storage of ACh?
AH5183 (vesamicol)
What does Mg2+ do to the presynapse?
It prevents Ca2+ entering the nerve terminal by blocking VOCC
What clinical uses does Botulinum toxin have?
‘Cosmetic’ medicine
Treats hyperhidrosis (excessive sweating)
Treats bladder hyper-reactivity
What happens to ACh after it is released?
Once released, a lot of ACh is degraded by acetylcholinesterase (AChE) which is found in the synaptic cleft.
The ACh that makes it to the postsynapse acts as an agonist to nicotinic acetylcholine receptors.
AChE breaks down ACh, how?
It breaks down ACh into acetyl and choline. It breaks the ester bond.
Describe the function and structure of the nicotinic ACh receptor.
It is activated by nicotine (nicotine is the agonist)
It is formed by five subunits (α,α,β,γ,δ) which form around a non-selective cation channel.
Channel opens when there are two ACh molecules, each bond to one α subunit.
What is the end plate potential?
The depolarisation of the muscle membrane produced following activation of the NAChR.
What does suxamethonium do?
Acts as an agonist at NAChR. Suxamethonium (succinylcholine) is not broken down by AChE so it lingers at the NMJ producing a prolonged depolarisation.
How is succinylcholine broken down?
Not acetylcholine, butyryl-cholinesterase or pseudo-cholinesterase break down succinylcholine.
What effects do anticholinesterase have?
The drugs prevent breakdown of ACh so effectively increase concentration of ACh. They reverse the effects of reversible competitive antagonist.
Where are the nicotinic activated receptors typically found?
They’re found on ganglia.
What are Muscarinic receptors?
They are G protein coupled receptors.
They are like NAChR but they’re more sensitive to muscarine in comparison to nicotine.
What is pilocarpine?
It is a mimic of ACh.
Muscarinic receptors….. Gq linked
.
Muscarinic receptors ….. Gi/o linked
.