Neuro - NTs and Pharmacology Flashcards
What features of the nervous system underpin synaptic transmission?
Diversity and plasticity of nervous system
What do spines on dendrites do?
Increase surface area
What are dendrites concerned with?
Information reception
What does the soma do?
Integration of multiple signals form different NTs
What is the axon/synaptic terminal involved in?
Rapid transmission of the AP and NT release
How fast is neurotransmission?
2ms
How wide is a normal synaptic cleft?
20-100nm
What are the 3 main stages of synaptic transmission?
1 Biosynthesis
2 Receptor action
3 Inactivation
What are the three main molecules that make up NTs?
Amino acids
Amines
Neuropeptides
What is an example of NTs that are amino acids
Glutamate
GABA
Glycine
What is an example of NTs that are amines
DA
NA
What is an example of NTs that are neuropeptides
opioid peptides e.g. endorphins
What kinds of effects do NTs evoke?
Rapid or slower effects
How many NT influences are received simultaneously by a neurone?
Multiple, which are then integrated into 1 diverse signal in the 2nd cell.
How are calcium channels opening in the presynaptic terminal?
From both a sodium influx and potassium efflux as a result of depolarisation from AP
What does the intracellular volume of calcium increase to?
from 1µM —-> 200µM
What does NT release depend upon?
Calcium dependent and rapid transduction
Is neurotransmission active or passive?
Active - requires ATP
How are synaptic vesicles filled with NTs?
Protein pumps pump from 4,000 to 10,000 NTs into a vesicle
What happens after the influx of calcium?
Vesicles containing NTs dock and are primed at the edge of the knob, but only release when they fuse with the membrane with the help of vesicular proteins.
What is the role of vesicular proteins?
Help the fusing of the vesicles with the membrane of the presynaptic terminal
What is an example of a vesicular protein?
SNARE proteins: synapsin
What is alpha latrotoxin?
Neurotoxin - stimulates NT release until the presynaptic neurone is depleted of NTs
Where is alpha latrotoxin found?
Black Widow Spider Venom - causes ACh release and eventual paralysis.
What are zinc dependent endopeptidases?
inhibit NT release
What is an example of a zinc dependent endopeptidase?
Tetanum toxin from C.Tetani - causes spasms and paralysis as it inhibits GABA and Glycine release which are inhibitory
Where is the botulinum toxin come from?
C.Botulinum
What is the effect of botulinum toxin?
Causes flaccid paralysis - first part of molecule binds to nerve terminal and the 2nd part penetrates the cholinergic terminal and cleaves the peptide bonds of vesicular proteins to inhibit NT release
How does botulism cause death?
Respiratory arrest
What is c.botulinum used for commercially?
Botox
What are the 2 main classes of receptor?
Ion channel linked
G-protein coupled
How fast do ion channel linked receptors act?
Fast (milsecs)
How fast do g-protein coupled receptors act?
Slow (seconds to minutes)
What do ion-channel linked receptors mediate?
All fast, excitatory and inhibitory transmissions
What do G-protein coupled receptors mediate?
All slow reactions
What may G-protein coupled receptors be in the form of?
Enzymes or channels
What is an example of an ion channel inked receptor?
Glutamate receptor - allows for the opening of sodium channels to allow for depolarisation and propagation of the AP.
How do G-protein coupled receptors work?
First couples to the G protein which then links to the effector to induce a response in the effector
What is an example of a G-protein coupled receptor?
ACh muscarinic receptors
What is the structure of ion channel inked receptors?
5 subunits with distinct properties on each one.
What is the glutamate receptor?
Excitatory ion channel inked receptor linked to depolarisation
What is the GABA-A receptor?
Inhibitory ion channel inked receptor linked to hyperpolarisation
What is the EPSP?
Excitatory post synaptic potential after the binding of glutamate
What is the IPSP?
Inhibitory post synaptic potential after the binding of GABA
What must there be between the EPSP and is the IPSP?
A balance
What is the AMPA receptor?
Type of glutamate receptor
What does the AMPA receptor mediate?
Majority of fast excitatory synapses
How is the AMPA receptor closely regulated?
Rapid onset, offset and desensitisation
What is the NMDA receptor?
Glutamate receptor that’s permeable to Calcium as well as Sodium
What do NMDA receptors do?
Provide the slow component of excitatory transmission
How do NMDA receptors serve as coincidence detectors?
Underlie learning and memory mechanisms (e.g. hippocampus has a high concentration of NMDA receptors)
How is glutamate produced?
By glucose via the TCA cycle and transamination in the presynaptic terminal.
How does glutamate act as a neurotransmitter?
Reversibly binds to post synaptic receptors to eventually induce a post synaptic response
What happens after glutamate binds to receptors?
It is inactivated by reputake into the presynaptic cells and glutamate transports found in glial cells + presynaptic terminal
What are EAATs?
Excitatory amino acid transporters
What is the glutamate-glutamine cycle?
Glutamate is converted to glutamine via glutamine synthetase. A high concentration of glutamine is then released by glial cells and pumped back into the presynaptic terminal
What is commonly associated with excess glutamate found within the synapse?
Seizures
How do things return to normal after a seizure?
Glutamate levels slowly fall as it is converted to glutamine
How is epilepsy characterised?
Recurrent seizures due to abnormal neuronal excitability
How many epilepsy patients are refractory to treatment?
25-30%
What do we believe to be the underlying problem with many cases of epilepsy?
GABA transmission (inhibitory) may not be functioning correctly allowing excess glutamate activity to occur
How is GABA synthesised?
Decarboxylation of glutamate via glutamic acid decarboxylase in the presynaptic terminal
How does GABA cause hyperpolarisation?
Binds to GABA-ARs to induce chloride influx into cells so that the cell is less sensitive to the Action potential, as its MP is brought down lots.
What happens to GABA after binding to GABA-A receptors?
Reuptake of GABA via GABA transporters (GATs) in presynaptic terminal or modification by GABATS
What are GABATs?
GABA transaminase which modified GABA to succinic semialdehyde which is the converted to succinate for the TCA cycle
Where does conversion of GABA to succinic semialdehyde take place?
Typically glial cells, but excess GABA in cells means that the presynaptic terminal will take up some GABA too with GABATS
What is the structure of a GABA receptor?
Pentameric
How are drugs tailored towards GABA receptor structure
Different drugs can bind got different sub units of GABA A receptor - many of them facilitate GABA transmission to improve its function.
What’s an example of anti-epileptic drugs?
Barbiturates