Neurotransmitters Flashcards
What are the types of neurotransmission in the CNS? What is the difference between them?
fast point to point signalling - neurotransmitters produce excitatory or inhibitory potentials - are ligand gated ion channels = activation takes milliseconds slow transmission - neurotransmitters and neuromodulators - are G protein couple receptors = activation induces a second messenger response and can takes seconds
What are the types of fast ligand gated ion channels and slow G protein coupled receptors?
glutamate - act on N-methyl-D-aspartate receptors (NMDAs) GABA (gamma-aminobutyric acid) - act on GABAa receptors acetylcholine - act on nicotinic receptors
monoamines = dopamine, serotonin
- act on dopaminergic and serotonergic receptors
peptide = opioids
- act on opioid receptors such as mu, delta and kappa
acetylcholine
- act on muscarinic receptors
What are the types of G proteins?
Gs - stimulates adenylyl cyclase Gi - inhibits adenylyl cyclase Gq - activates phospholipase C Go - inhibits calcium and potassium channels G12 - activates RhoA kinase
How is glutamate synthesised and released?
glutamate is synthesised from glutamine during an enzymatic reaction in the neurone
- enzyme glutaminase catalyses the conversion
glutamate is stored in vesicles and when the neurone is stimulated, it gets released into the synaptic cleft
acts on glutamate receptors to excite neighbouring neurones
Where does glutamine come from?
glutamine comes from food and is a product of glucose (Krebs cycle)
How is glutamate regulated?
action of glutamate is terminated by reuptake of glutamate via glutamate transporters back into neurones or into glial cells (astrocytes)
astrocytes have excitatory amino acid transporters (EAAT) which take up glutamate
- converts glutamate back into glutamine via glutamine synthase
- glutamine is excreted out by glutamine transporters (GluT) and taken into neurones
excitatory amino acid transporters (EEAT) are also found on the neurones themselves
- they regulate glutamate by reuptake into the neurone
Why must glutamate concentration be regulated?
- effect of too little and too much
if too much glutamate is released
- can cause hyperexcitability of neighbouring neurones which leads to excitotoxicity and cell death
= can result in strokes and epilepsy
if too little glutamate is released:
- can under excite cells
= can result in memory loss, learning difficulties and schizophrenia
What is the structure of glutamate receptors? How do they act?
are two types of glutamate receptors
- ligand gate ion channels = NMDA, AMPA and kainite
- metabotropic receptors (GPCR)
How does glutamate act on NMDA receptors? What other substances can act on NMDA receptors?
glutamate is an excitatory neurotransmitter
- binds to NMDA
- channel opens and positively charged ions enter the neurone = sodium, calcium, potassium
- causes depolarisation
NMDA is highly permeable to calcium ions but at resting potential, its action is blocked by, magnesium ions
- when the cell is depolarised, magnesium moves out and allows calcium flow in
some anaesthetics (ketamine) and psychotomimetic (phencyclidine) drugs block the channel - channel blocking drugs
glycine can bind (inhibitory)
- means glycine antagonists can bind
What effect do NMDA agonists have?
stimulating NMDA receptors in the hippocampus is important for synaptic plasticity
- activation in the hippocampus increases synaptic connectivity
= enhances cognitive behaviour (memory), learning
Why must NMDA agonism be regulated?
- effect of too little and too much
hyperstimulation can cause:
- epilepsy, stroke, depression, ADHD, antipsychotic, neuropathic pain
hypostimulation can cause:
- antiepileptic, schizophrenia, loss of memory and antidepressant
What is acetylcholine? Where are cholinergic neurones found?
acetylcholine is a monoamine released from cholingeric neurons
- is a excitatory neurotransmitter
cell bodies of cholinergic neurones reside in
- the nucleus basalis and project into corticol regions (regions of the cerebral cortex) where acetylcholine is released
- the septum and project into the hippocampus where acetylcholine is released
- the striatum
- the substantia nigra and project into the thalamus where acetylcholine is released
How is acetylcholine synthesised?
acetylcholine is produced from acetyl CoA and choline by choline acetyl transferase (CAT)
- Ach then enters cholinergic vesicles
- the vesicles are recruited to the membrane and released into the synaptic cleft via exocytosis
Ach acts on
- nicotinic receptors opening ligand gated ion channels resulting the influx of sodium ions
- muscarinic channels which have slow transmission as they are metabotropic receptors (GPCR)
How is acetylcholine broken down?
acetylcholine is broken down into choline and acetate by enzyme acetylcholinesterase (AchE)
- choline and acetate will re-enter cholinergic neurone via choline transporters (choline carriers)
What are the functions of acetylcholine?
arousal
epilepsy - mutations of nicotinic Ach receptors genes
learning and memory
- inhibition of acetylcholinesterase (AchE) improves memory and treats dementia/Alzheimers’s
pain
addiction
motor control - muscarinic receptors inhibit DA
= involved in the treatment of Parkinson’s disease and schizophrenia
involved in ADHD, depression, anxiety
