Neurotransmitter Flashcards
What is neurotransmission? – BASICS.
It is the information transfer between two neurones across a synapse. It occurs when neurotransmitters interact with post synaptic receptors.
Recap: what is the role of the soma in a neurone in transmission of an impulse?
Integration of all the inputs to produce a single response. Some of these inputs may be direct inputs – important for controlling the neurone. [Already covered in cells of the nervous system.]
How fast is chemical neurotransmission?
200us – time of the synapse.
Recap: what are the three structures in a synapse and what is there function? How large is one of the components?
Presynaptic nerve ending – releases the neurotransmitter. Synaptic cleft – high resistance to transfer of electric charge and is between 20 and 100 nm. Postsynaptic region – the receptive area on the dendrite or soma.
What organelle is in high abundance in the pre-synaptic terminal? Why?
Mitochondria – chemical neurotransmission is a highly energy independent process.
What is the postsynaptic density?
Is identified by electron microscopy as an electron-dense region of the postsynaptic membrane. It is a protein dense region. This is needed in the signalling pathways to regulate the activity of the downstream cell.
What is meant by a synapse being asymmetric?
The direction of the impulse is unidirectional.
What are the three stages of synaptic transmission?
- Biosynthesis, packaging and release of neurotransmitter. 2. Receptor action. Usually, an action potential is generated. 3. Inactivation.
What gives neurotransmitters such variety? Examples? (x3 (x3, x2, x1) [Don’t need to know the specific examples, but glutamate and GABA are probably good ones to remember.]
There are a variety of chemicals that they can be made up of. AMINO ACIDS: most common is glutamate (or glutamic acid), GABA (major inhibitory neurotransmitter in the CNS), glycine. AMINES: noradrenaline and dopamine. NEUROPEPTIDES: opioid peptides.
Summary: what are the basic activities occurring in a synapse? (x4) IMPORTANT.
Action potential depolarises the presynaptic membrane. Triggering calcium entry which causes neurotransmitter release into the synapse. Neurotransmitter removed to stop the action ongoing. This is carried out by a class of molecule called a transporter. High levels of potassium also need to be pumped out of the synapse by an ATP dependent pump, back into the pre-synaptic cell.
What is the mechanism of neurotransmitter release into the cleft called?
Mechanism: ELECTRO-MECHANICAL TRANSDUCTION. It is the conversion from an electrical (depolarisation of membrane and opening of calcium channels) to a mechanical (calcium influx, vesicle exocytosis) mechanism of transmission.
What is the mechanism of neurotransmitter release?
Membrane depolarisation. Ca2+ channels open. Ca2+ INFLUX. Vesicle fusion with pre-synaptic membrane. Vesicle exocytosis. Transmitter release.
Describe the process of neurotransmitter release in relation to the proteins involved.
Many proteins involved in the process. Some are localised to the synaptic vesicle (in red). Others lie on the pre-synaptic membrane (dark green). A protein complex forms between the proteins on the vesicle and the proteins in the pre-synaptic membrane. When this complex is formed, the vesicle is ‘primed’ to the ‘active zone’, meaning that the neurotransmitter is ready for release as soon as the action potential arrives. The fact that they are docked before any action potential arrives, makes transduction as fast as possible. Action potential means that voltage-gated calcium channels open. Calcium influx activates a Ca2+ sensor in the protein complex which causes a conformational change which promotes fusion of the vesicle and the membrane = opening a pore that releases the neurotransmitter = exocytosis.
Why is the protein complex between the vesicle and membrane so stable?
They form a stable complex because of overlap in the alpha helical tails between the vesicle and membrane proteins.
What is relevant about the nature of calcium influx that makes neurotransmission as fast as possible?
Calcium channels found in very close proximity to the primed vesicles – as shown in the photo. Calcium concentration increase only needs to happen LOCALLY, for it to bind to the calcium sensor and stimulate exocytosis.
What toxins are the vesicular proteins vulnerable to? (x3) What are the referred to as?
[Not really required knowledge – not in specification. Although mechanisms of termination are a point on Sofia – so maybe learn mechanism, but don’t fuss about remembering toxin names.] Referred to as neurotoxins. Examples: TETANUS toxin (targets vesicular proteins), BOTULINUM toxin (targets vesicular and membrane proteins), and alpha LATROTOXIN TETANUS AND BOTULINUM BLOCK NEUROTRANSMITTER RELEASE. Alpha Latrotoxin prevents vesicles from being repackaged with neurotransmitter after release – so neurotransmitters are depleted to exhaustion.
What are the two types of neurotransmitter receptor?
REMEMBER, these are receptors found on the post-synaptic membrane and initiate or prevent a response in the post-synaptic area! Ion channel receptor. G-protein coupled receptor.
What is the difference in actions between the ion channel and G-protein coupled receptors?
ION CHANNEL RECEPTORS: mediate FAST excitatory and inhibitory transmission. G-PROTEIN COUPLED RECEPTORS: mediate SLOW transmission.
How do G-protein coupled receptors work in response to neurotransmitter binding?
They transduce effects between the receptor and an effector. Effectors include enzymes (e.g. adenyl cyclase) OR channels (e.g. Ca2+). Results in increase of cAMP, which is a second messenger that stimulates a response in the pathway. Remember, not all responses in the post-synaptic region have to be neuronal – they can be chemical e.g. muscular contraction.
What examples are there of receptors for each type? (x3 and x3)
ION CHANNEL: Glutamate receptors (GLUR) (CNS), GABA receptors (CNS), Ach receptors (NMJ). G-PROTEIN COUPLED RECEPTOR: Ach in muscarinic receptors, dopamine, noradrenaline. (all CNS and PNS).
What is the difference in the mechanisms between an excitatory and inhibitory neurotransmitter ION CHANNEL receptor? Example of receptor for each?
EXCITATORY: opens pore which allows Na+ influx = generation of an EPSP – Excitatory postsynaptic potential. DEPOLARISATION! e.g. Glutamate receptor. INHIBITORY: opens pore which allows Cl- influx into post-synaptic cell = generation of an IPSP – Inhibitory postsynaptic potential. HYPERPOLARISATION! e.g. GABA receptor.
What are the two main types of glutamate receptor?
AMPA receptor and NMDA receptor.
What are the differences between the two glutamate receptor subtypes? (x2 and x6)
AMPA receptors, when stimulated, allow flow of Na+ into the post-synaptic neurone. Activated for a FAST excitatory synapse with rapid onset, rapid offset, and rapid desensitisation (effect of neurotransmitter diminishes rapidly). NMDA receptors only operates on a cell that has already been depolarised. The receptor, when stimulated, opens a channel for Na+ AND Ca2+. Mediates slow excitatory transmission and is able to change the response of the AMPA receptor. It is also able to change transcription and help form new synapses. These receptors underly learning mechanisms.
How does the NMDA receptor potentiate the AMPA receptor response?
By calcium activated phosphorylation of the AMPA receptor.
How are neurotransmitters removed and re-absorbed generally?
By a class of proteins called Transporters. They are taken up by the neurone. Or the glial cells where they are metabolised.
How are glutamate receptors (GLUR) inactivated?
Excitatory amino acid Transporter (EAAT) takes up glutamate rapidly into the pre-synaptic neurone and glial cell from the synapse. The transporter is located on the membranes of these cells. In the glial cell, the glutamate is metabolised by glutamine synthetase which gives glutamine. Glial cell is main site for inactivation of glutamate.
What is epilepsy characterised by?
Characterised by recurrent seizures due to abnormal neuronal excitability. Abnormal activity arises from decrease in GABA-mediated inhibition or an increase in glutamate-mediated excitation in the brain.
How is GABA synthesised?
Synthesised by removal of COOH group from the Glutamate neurotransmitter. Turns neurotransmitter from excitatory to inhibitory. Catalysed by Glutamic acid decarboxylase (GAD), which is highly concentrated in the nerve terminal and GABA neurones.
How are GABA receptors inactivated? Special property of metabolite?
GABA is removed from the synapse by the GABA transporter (GAT). Found on glial and pre-synaptic cells. GABA is metabolised in a single-step reaction by GABA transaminase (GABA-T), which produces Succinate semialdehyde which feeds into the TCA cycle.
Why are GABA receptors of pharmacological interest?
GABA receptors are a pentameric receptor – so made of 5 sub-units as shown in the picture. Drugs have been developed to enhance GABA transmission and its inhibitory effects.
Useful in epilepsy. Epilepsy treatment is focused on damping down excitatory activity by facilitating inhibitory transmission.
How have drugs been designed to facilitate the effects of GABA? (x3)
GABA binds to the pentameric complex, opening the Cl- channel. Drugs have been designed to facilitate this action by modifying the receptor at a number of allosteric sites (shown in the photo). These drugs increase the frequency the channel opens when the GABA binds to it. So, drugs enhance GABA and its inhibitory effects.
Drugs may also inhibit GABA transaminase or inhibit GABA reuptake.
List four drugs that target allosteric sites on the GABA receptor, used to treat epilepsy.
Benzodiazepines, Phenobarbital, Vigabatrin, Tiagabine.
What are the two classes of epilepsy?
Generalised epilepsies (or seizures) and partial epilepsies (or seizures). GENERALISED: abnormal neuro-transmission in the whole brain which all results in loss of consciousness. PARTIAL: abnormal neuro-transmission occurs in small part of the brain.
What are the types of generalised (x4) and partial (x3) epilepsies, and their clinical features?
GENERALISED:
Tonic-clonic – unconscious, muscle extension (tonic) followed by muscle contraction (clonic). Absence – Short-lived. Characterised by zoning out (still considered loss of consciousness) OR jerking (with loss of consciousness). Myoclonic – exaggerated twitch of area of the body. Atonic – short-lived loss of muscle tone which results in individual falling over flat suddenly.
PARTIAL:
Simple – uncontrolled twitched of one part of the body – no loss of consciousness. Complex – affects the temporal lobe and most difficult to treat. Results in loss of awareness, confusion, and unusual behaviours and gestures. Secondary generalised – generalised seizures develop from a partial one.
