Chemical Signalling Flashcards
What are the types of neurotransmitter?
amino acids
monoamines
acetylcholine
neuropeptides
What are the types of neurotransmitter?
amino acids
monoamines
acetylcholine
neuropeptides
What are amino acids?
chains of proteins e.g. GABA and glutamate (responsible for fast transmission)
What are examples of monoamines?
dopamine and serotonin
Where are acetylcholine’s synthesised and stored?
they are synthesised in the presynaptic terminal and stored in synaptic vesicles
When are acetylcholine’s released?
when there is a local increase in Ca2+
Where are neuropeptides synthesised and released?
they are synthesised in the cell soma and transported to the terminal where they are stored in secretory granules
When are neuropeptides released?
when there is a global increase in Ca2+
Give an example of a neuropeptide
endorphins
What are amino acids?
chains of proteins e.g. GABA and glutamate (responsible for fast transmission)
What are examples of monoamines?
dopamine and serotonin
Where are acetylcholine’s synthesised and stored?
they are synthesised in the presynaptic terminal and stored in synaptic vesicles
When are acetylcholine’s released?
when there is a local increase in Ca2+
Where are neuropeptides synthesised and released?
they are synthesised in the cell soma and transported to the terminal where they are stored in secretory granules
When are neuropeptides released?
when there is a global increase in Ca2+
Give an example of a neuropeptide
endorphins
What are the criteria for neurotransmitters?
chemically synthesised presynaptically
electrical stimulation leads to the release of a chemical
chemical produces physiological effect
terminate activity
How is glutamate synthesised?
it is synthesised from glucose or glutamine in the nerve terminals
How is glutamate stored?
it is loaded and stored in vesicles by vesicular glutamate transporters
How is glutamate released?
exocytosis
What is neuromodulation?
alteration of the presynaptic cell’s ability to release neurotransmitter or the postsynaptic cell’s ability to respond
What is the reuptake mechanism for glutamate?
excitatory amino acid transporters reuptake glutamate in the plasma membrane of presynaptic cell and surrounding area
What can too much glutamate/too little GABA cause?
hyperexcitability (epilepsy) or excitotoxicity
What is cerebral ischemia?
insufficient blood flow in the brain caused by plaques/tumors
What are some symptoms of ischemia?
weakness
visual impairment
release of glutamate
excitotoxic cell death
What is an agonist?
a drug which can combine with a receptor on a cell to produce a cellular reaction
What is an antagonist?
a drug that reduces or completely block the activity of the agonist, no cellular effect after interacting with a receptor a.k.a. endogenous ligand
What is an excitatory post synaptic potential?
glutamate ionotropic receptors flux Na+ depolarising the postsynaptic neuron
What is an inhibitory post synaptic potential?
GABA ionotropic receptors flux Cl- hyper polarising the postsynaptic neuron
What happens at an AMPA receptor?
an ionotropic receptor
the binding of glutamate leads to the opening of a Na+ channel and hence depolarisation
has slight K+ permeability
a fast opening channel
What are the features of an NMDA receptor?
an ionotropic receptor voltage dependent blockade permeable to Na+, K+, Ca2+ slow opening channel requires glutamate and glycine (cofactor) to open the gate
What can be caused by the dysregulation of NMDA?
Schizophrenia symptoms
How do we know NMDA receptors are linked with schizophrenia?
phencyclidine and MK801 block NMDA receptors and produce schizophrenia like symtpoms
What happens during glutamate exciotoxicity?
excessive Ca2+ influx activates calcium dependent proteases and phospholiphases which damage the cell
Where is GABA stored?
it is loaded and stored into synapses by a vesicular GABA transporter
How is GABA synthesised?
from glutamate
When is GABA released?
during excytosis (Ca2+ dependent)
Where does GABA act?
ionotropic GABAa receptor
metabotropic GABAb receptor
both are on the postsynaptic membrane
How is GABA cleared from the synapse?
reuptake using transporters on glia and neurons including non-GABAergic neurons
What are the effects of too much GABA?
sedation/coma
anxiolytic
What are 2 features of the ionotropic receptors?
GABA ligand gated Cl- channels
fast IPSP’s
What is a feature of metabotropic receptors?
slow IPSP’s
What does GABA do?
increase the permeability of Cl- and hypolarises the neuron
What is an indirect agonist?
An agonist which only works in the presence of a particular neurotransmitter
What do barbiturates do?
enhance the effect of GABA
general depression of neuronal activity
What are some risks involved with barbiturates?
small difference between therapeutic dose and overdose
high suicide risk
can lead to dependence and withdrawal
What can benzodiazepines be used for?
fast acting anxiolytics anticonvulsant sedative muscle relaxant amnestic
What is some evidence for GABAergic dysfunction in anxiety disorders?
patients with panic disorder are shown to have less benzodiazepine binding sites
What is a diffuse modulatory system?
populations of neurons that project diffusely and modulate the activity of glutamate and GABA neurons in their target areas
What is the function of dopamine?
its is the pleasure/reward molecule which projects into the forebrain
What is the nigrostriatal system’s involvement in dopamine?
the substantia nigra projects dopamine onto the neostratium which is involved in movement
What effect does Parkinson’s disease have on dopamine?
it destroys the dopamine projections from the substantia nigra to the basal ganglia
What effect does Huntington’s disease have on dopamine?
destroys the target dopamine neurons in the striatum
What is the mesolimbic system’s involvement in dopamine?
the ventral tegmental area projects dopamine to the nucleus accumbent, this is involved in reinforcement and reward
What happens withe dopamine during addiction?
drug abuse can lead to enhanced dopamine release in the nucleus accumbens
What is the mesocortical system’s involvement in dopamine?
the ventral tegmental area projects dopamine to the prefrontal cortex, involved in working memory and planning
How is dopamine synthesised?
tyrosine is converted into L-Dopa and then dopamine
What is tyrosine and how is it catalysed?
it is an essential amino acid obtained through diet which is catalysed by tyrosine hydroxylase
How is L-Dopa catalysed?
by dopa decarboxylase
How is tyrosine hydroxylase reduced?
dopamine is competing for binding with an essential cofactor, too much dopamine lowers the tyrosine hydroxylase activity
How is tyrosine hydroxylase activity increased?
presynaptic activity leads to the phosphorylation of TH increasing its activity
prolonged activity leads to an increase in TH gene transcription
What effect does reserpine have on dopamine synthesis and storage?
impairs the storage of monoamines in synaptic vesicles leaving them empty
What effect do amphetamines/methylphenidates have on dopamine synthesis and storage?
psychostimulants which block the reuptake of monoamines into the terminals so there is more dopamine in the synaptic cleft extending its action
What effect does > selegiline/entacapone have on dopamine synthesis and storage?
prevents the breakdown of catecholamines increasing the releasable pool available
How is dopamine released?
depolarisation of the presynaptic membrane
influx of Ca2+ through voltage gated channels
Ca2+ dependent vesicle docks to the membrane and releases the neurotransmitter
What does the noradrenergic system control?
arousal and attention
What can noradrenergic dysfunction lead to?
anxiety and depression
What does the serotonergic system control?
appetite, pain, sleep and emotions
How is serotonin synthesised?
tryptophan is converted into 5-hydroxytryptophan and then serotonin
How does fluoxetine affect the serotonin system?
blocks the reuptake of serotonin and is used as an antidepressant/anti-anxiety medication
How does fenfluramine affect the serotonin system?
induces the release of serotonin in the synaptic cleft and inhibits its reuptake used as an appetite suppressant
How does MDMA affect the serotonin system?
causes transporters to run backwards releasing serotonin into the synapse
What is acetylcholine synthesised from?
choline
Where is acetylcholine stored?
in vesicles
How is acetylcholine metabolised?
it is rapidly degraded in the synaptic cleft by acetylcholinesterase into choline
How is acetylcholinesterase synthesised?
by the cholinergic neuron, secreted into the synaptic cleft and associated with the axonal membrane
What to acetylcholinesterase inhibitors do?
block the breakdown of acetylcholine thus prolonging its action in the synaptic cleft
What do botulinum and tetanus toxins do?
block the docking of vesicles by attacking SNARE proteins
What does botox do?
acts at the euro-muscular junction causing the muscles to lose all input and become permanently relaxed
What is the action of the tetanus toxin?
inhibits the release of glycine, disinhibiting the cholinergic neurons so they continuously fire causing permanent muscle contraction
What is a disorder associated with the peripheral cholinergic system?
myasthenia gravis; an autoimmune disease which destroys cholinergic receptors in the muscle
What is the cholinergic systems role in Alzheimer’s disease?
loss of cholinergic neurons in the basal ganglia, underlies deficits in in memory
