neurotransmitters and pharmacology Flashcards by Rumaysa Ahmed

what does information transfer across a synapse require

a neurotransmitter and their interaction with postsynaptic receptors

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summarise synaptic transmission in 4 steps

1) NT release from 1st cell
2) synaptic activation of 2nd cell
3) signal integration and signal conduction by 2nd cell
4) signal transmitted to effectors or subsequent neurones

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4 features of synaptic transmission

rapid timescale
diversity of CNS function
plasticity
learning and memory

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what is the structure of a neuron and how does it relate to synaptic transmission

dendrite (spines where info is received)
soma (body where info is integrated)
axon and synaptic terminals (where info is transferred rapidly by AP)

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what is the soma

cell body

every neurone has one

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what is the end of the axon called

synaptic terminal

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what do dendrites have that increase SA for info receiving

proteins called spines

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what does the cell body do

integrate info

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what is AP

electrical transmission

chemical transmission occurs at the synaptic cleft

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how big is the synaptic gap/cleft

20-100nm

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STEPS for NT (3)

1) biosynthesis, packing and release of NT
2) NT released by exocytosis and receptor action on post synaptic neuron
3) inactivation of NT after activation on receptor

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what are 3 types of NTs within the central nervous system

amino acids
amines
neuropeptides

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examples of amino acid neutrotransmitters

gluatamate
GABA
glycine

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examples of amine neurotransmitters

noradrenaline

dopamine

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examples of neuropeptide neurotransmitters

opioid peptides

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STEPS for activation of a CNS synpase

1) arrival of AP
2) spreads across nerve terminal
3) activates depolarisation of entire nerve terminal (rapid Na+ influx and K+ efflux) which activates VGCCs > Ca2+ enters and goes to nerve terminal > activates exocytosis of vesicle with NT
4) released into the cleft
5) rapidly diffuses across gap down gradient
6) binds to receptors on postsynaptic membrane > excitatory synapse as receptors allow influx of Na+ into postsynaptic cell > depolarisation of postsynaptic cell and generation of another AP > passes down axon
7) NT generated response > inactivate rapidly (reuptake of NT)
8) activation of Na+/K+ pump > extrudes Na+ that came in and replaces it with K+ (functions independently of reuptake system)
9) or enzyme degradation in cleft eg acetylcholinesterase to break down acetylcholine

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where is acetylcholinesterase found

bound to basolateral membrane in synaptic cleft

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what does neurotransmitter release need

an increase in intracellular Ca2+ as it is calcium dependent

requires rapid transduction

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what is electromechanical transduction

links opening of calcium channel > influx > NT release into cleft

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SUMMARY of NT release

membrane depolarisation
Ca2+ channels open
Ca2+ influx
vesicles are primed
vesicle fusion
vesicle exocytosis
NT release

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where are synaptic vesicles filled with NT docked

into synaptic zone

what enables vesicle fusion and exocytosis on vesicles and presynaptic membranes

special proteins

eg SNARE proteins (vesicular proteins) mediating process of exocytotic release of NT

what are targets for neurotoxins

vesicular proteins

example of neurotoxin = alpha latrotoxin

black widow spider
stimulates NT release to depletion
binds to cholinergic terminal and causes release of ACh until depletion leading to muscular paralysis

example of neurotoxin = Zn2+ dependent endopeptidases

inhibit NT release eg tetanus toxin (inhibits GABA release and glycine release leading to spasms and paralysis)

example of neurotoxin = botulinum toxin

C botulinum - generating botulinum toxin > can cause arrest causes flaccid paralysis made of 2 chains 1st chain binds to cholinergic nerve terminal 2nd chain penetrates the cholinergic nerve terminal and interacts with vesicular proteins cleaves peptide bonds of vesicular proteins can no longer dock/fusion/release of NT - inactivated

what are the 2 main groups of receptors

ion channel linked receptors (FAST) | G protein coupled receptors (SLOW)

what are ion channel linked receptors and examples

receptors that produce fast response mediate all fast excitatory and inhibitory transmission glutamate binds to receptor > stimulation > opening allowing influx of Na+ into cell > AP GABA (CNS) neuromuscular junction - ACh at nicotinic receptors

what are G protein coupled receptors

slow response effectors may be : - enzymes (adenyl cyclase, phospholipase C, cGMP-PDE) - channels (eg Ca2+/K+) examples CNS and PNS : ACh at muscarinic receptors, dopamine (DA), noradrenaline (NA), serotonin (SHT) and neuropeptides (eg enkephalin)

how do G protein coupled receptors work (STEPS)

1) stimulated by agonist 2) bind to G protein in membrane 3) G protein couples to receptor 4) second messenger in cell

features of ion channel linked receptors

rapid activation rapid info flow multiple subunit combinations > distinct functional properties

what is the ion channel linked receptor for acetylcholine

nicotininc cholinergic receptors (nAChR)

what is the ion channel linked receptor for glutamate

GluR

what is the ion channel linked receptor for GABA

GABAR

what is the ion channel linked receptor for glycine

GlyR

how many subunits are there

around 5

GABA A receptors are..

inhibitory

glutamate receptors lead to..

depolarisation

STEPS for excitatory NT receptor

eg glutamate receptor release of glutamate activating receptor on postsynaptic membrane rapid influx of Na+ through channel (sometimes through receptor itself) down EC gradient shoots into postsynaptic nerve generates EXCITATORY POSTSYNAPTIC POTENTIAL (EPSP)

STEPS for inhibitory NT receptor

eg GABA binds to GABAR opens Cl- channel Cl- enters fall in membrane potential (hyperpolarisation) leads to INHIBITORY POSTSYNAPTIC POTENTIAL

what exists between GABA and glutamate

a balance in the brain

what are the 2 types of glutamate receptors

AMPA receptors | NMDA receptors

describe AMPA receptors

majority of FAST excitatory synapses | rapid onset, offset and desensitisation

describe NMDA receptors

slow component of excitatory transmission | serve as coincidence detectors which underlie learning mechanisms

STEPS for excitatory glutamate synapse

1) glutamate synthesised from glucose via TCA cycle and transamination 2) glutamate reversibly binds postsynaptic receptors (linked to ion channels) 3) rapid uptake of glutamate by excitatory amino acid transporters (EAATs) excitatory AA transporters 4) glutamate enzymatically modified by glutamine synthetase to glutamine in glial cells

what receptors are found in the hippocampus

NMDA receptors

what are seizures

abnormal cell firing > seizures associated with excess glutamate in synapse glutamate returns to normal levels > increase in glutamine levels (metabolised glutamate)

what is epilepsy

characterised by recurrent seizures due to abnormal neuronal excitability disease can be disabling 25-30% refractory to treatment new gen of drugs targeting GABA synapse

STEPS for inhibitory GABA synapse

1) GABA synthesised by decarboxylation of glutamate by glutamic acid decarboxylase (GAD) 2) GABA reversibly binds postsynaptic receptors (linked to ion channels) 3) rapid uptake of GABA by GABA transporters (GATs) GABA enzymatically modified by GABA transaminase (GABA-T) to succinic semialdehyde (glial cells and GABA nerve terminals)

what does GABA do to action potentials

reduce AP frequency | harder to induce AP

structure of GABA receptor

pentameric organisation of GABA receptor > pharmacologically important binding domains

what are some drugs facilitating GABA transmission

``` antiepileptic anxiolytic - reduce anxiety sedative muscle relaxant enhance GABA inhibitory action ```