Neurotransmitters and Pharmacology Flashcards
What is synaptic transmission?
Information transfer across the synapse requires the release of neurotransmitter and their interaction with postsynaptic receptor
- Transmitter release from 1st cell
- Synaptic activation of 2nd cell
- Signal integration and signal conduction by 2nd cell
- Signal transmitted to effectors or subsequent neurones
How many synapses does each neurone recieve and make?
Several hundreds and thousands
How large is the synaptic cleft?
about 20-100 nm
What are examples of neurotransmitters?
Amino acids such as glutatamate, GABA, glycine
Amines e.g. noradrenaline and dopamine
Neuropeptides e.g. opioid peptides
How many NT molecules are there per synaptic vesicle?
About 4000 - 10000
How are NT’s released?
Ca2+ influx gives rise to docking (synaptic vesicles filled with NT)
Vesicles are docked onto presynaptic membrane and primed then undergo fusion
The vesicle then undergoes exocytosis
Empty vesicles bud off and are recyled- new vesicles formed
What are vesicular proteins?
They’re targets for neurotoxins
What are examples of neurotoxins?
Alpha latrotoxin (from black widow spider) stimulates transmitter release to depletion
Zn2+ dependent endopeptidases: inhibit NT release
Tetanus toxin (C tetani): causes spasms and paralysis
Botulinum toxin (c botulinum): causes flaccid paralysis (paralysis due to complete muscle relaxation) by inhibiting release of ACh- is injected in botox
What are the 2 types of NT receptors?
Ion channel linked receptor
G-protein coupled receptor
How does an ion channel linked receptor work?
Mediates fast responses
Mediates all fast excitatory and inhibitory transmission
Glu binds to receptor, stimulates receptor and allows it to open- influx of Na+ and generation of AP
Excitatory ion linked channel open Na+ channels in same was as Glu opens channel
Inhibitory ion linked channel usually opens Cl- channels
How does a G- protein coupled receptor work?
Mediates slow responses
Effectors may be enzymes (adenyl cyclase, phospholipase C, cGMP-PDE) or channels (Ca2+ for example)
G protein coupled receptor has 7 transmembrane (7-TM) segments
When stimulated by agonist (NT) it activates G protein in membrane
G protein couples to effector which changes production of cAMP
What are examples of ion channel linked receptors?
CNS: glutamate, GABA
Neuromuscular junction: ACh at nicotinic receptor
What are examples of G- protein coupled receptors?
CNS and PNS: ACh at muscarinic receptors, dopamine, noradrenalin, seretonin, neuropeptidases (e.g. enkaphalin)
What is an excitatory postsynaptic petential (EPSP)?
Influx of an ion causes an increase in membrane potential
What is an inhibitory postsynaptic potential (IPSP)?
Influx of ions into postsynaptic cell causes decrease in membrane potential
What is a glutamate receptor?
Ion lcannel linked receptor- excitatory
2 types:
AMPA receptor
NMDA receptor
What is an AMPA receptor?
Mediates majority of fast excitatory synapses
Have rapid onset, offset and desensitisation
What is an NMDA receptor?
Mediates slow component of excitatory transmission
Serve as coincidence detectors which underlie learning mechanisms
What process occurs at a Glu synapse?
Glutamate synthesised from glucose via TCA cycle and transamination and loaded into vesicles
Glu released and binds to postsynaptic recemptors (NMDA and AMPA)
Gu is inactivated and reuptaken in presynaptic terminal or by glial cells through excitatory amino acid transporters
In glial cell, glu is enzymatically modified by glutamate synthetase to glutamine
What causes seizures?
A balance needs to be maintained between glutamate and GABA
If theres too much synaptic glutamate we see increase spiking on ECG
This abnormal cell firing can lead to seizures
What is epilepsy?
Characterised by recurrent seizure activity due to abnormal neural excitability (overactivity and uncontrolled glutamate activity)
Drugs which target GABA synapse are used
What is a GABA receptor?
inhibitory receptor
Opens chloride channel
Influx of Cl- leads to hyperpolorisation
What happens at an inhibitory GABA synapse?
GABA synthesised by decarboxylation of glutamate by glutamic acid decarboxylase (GAD)
GABA loaded into vesicles and releasedinto cleft
GABA binds to GABA A receptors and opens a chloride channel- Cl- influx and hyperpolorisation in post synaptic cell
GABA is inactivated by reuptake by GABA transporter (GATs)
OR GABA is taken up by glial cellsand enzymatically modified by GABA-transaminase to succinic semialdehyde
How is GABA receptor structured?
Pentameric organisation of GABA receptor provides pharmacologically important binding domains
