Neurotransmission Flashcards
What is synaptic transmission?
Information transfer across the synapse requires release of neurotransmitters and their interaction with postsynaptic receptors
What is the general process of synaptic transmission?
- Transmitter released from 1st cell
- Synaptic activation of 2nd cell
- Signal integration and signal conduction by 2nd cell
- Signal transmitted to effectors or subsequent neurones
What are the 3 main processes of synaptic transmission?
- Biosynthesis, packaging and release of neurotransmitter
- Receptor action at post synaptic terminal
- Inactivation of neurotransmitters
What ion is neurotransmitter dependent on?
Calcium 2+
What is the process of neurotransmitter release?
- Membrane depolarisation
- Ca2+ channels open
- Ca2+ influx
- Vesicle fusion with membrane
S. vesicle exocytosis
What allows for the rapid transduction?
Special proteins on the vesicle and pre-synaptic membrane enable fusion & exocytosis
What is a vesicular protein?
membrane protein that regulates or facilitates the movement of specific molecules across a vesicle’s membrane
What can reticular proteins be targets for?
Neurotoxins
What are some examples of vesicular proteins + pre-synaptic proteins?
Vesicular: → SNARE proteins → synaptobrevin Pre-synaptic: → syntaxin → SNAP25
What are some examples of neurotoxins and their effects?
- Alpha latrotoxin (from black widow spider) stimulates transmitter release to depletion
- Zn2+ dependent endopeptidases inhibit transmitter release
- Tetanus toxin C tetani causes paralysis
- Botulinum toxin C botulinum causes flaccid paralysis
What is the purpose of ion channel-linked receptor?
- FAST response (msecs)
* Mediate all fast excitatory and inhibitory transmission
What are some examples of ion channel-linked receptors?
- nicotinic cholinergic receptors (nAChR)
- glutamate (GluR)
- gamma amino butyric acid (GABAR)
- glycine (GlyR) receptors
What is the purpose of G-protein-coupled receptors?
- Slow response (secs/mins)
* uses effectors (enzymes or channels) to get the job done
What neurotransmitters do ion channel-linked receptors interact with?
CNS: Glutamate, y-aminobutyric acid
NMJ: Acetylcholine (ACh) at nicotinic receptors
What neurotransmitters do G-protein-coupled receptors interact with?
CNS + PNS: Ach at muscarinic receptors, dopamine, noradrenaline, serotonin + neuropeptides
What neurotransmitter can produce an excitatory post synaptic potential? How?
Glutamate → causes influx of Na ions → causes post synaptic membrane depolarisation
What neurotransmitter can produce an inhibitory post synaptic potential? How?
GABA or glycine → influx of Cl ions → causes hyperpolarisation of post synaptic membrane
How does an excitatory CNS synapse work?
- Glutamate is synthesised from glucose in the Krebs cycle & transamination
- Glutamate reversibly binds post-synaptic receptors (linked to ion channels)
- Rapid uptake of glutamate by excitatory amino acid transporters (EAATs)
- Glutamate is enzymatically modified by glutamine synthetase to glutamine in glial cell
What are 2 examples of glutamate receptors?
- AMPA
* NMDA
What are AMPA receptors?
- Majority of FAST excitatory synapses
* Rapid onset, offset and desensitisation
What are NMDA receptors?
- Slow component of excitatory transmission
* Serve as coincidence detectors which underlie learning mechanisms
How does an inhibitory CNS synapse work?
- GABA is formed by decarboxylation of Glutamate by glutamic acid decarboxylase (GAD)
- GABA reversibly binds to post-synaptic receptors (linked to ion channels)
- Rapid uptake of glutamate by GABA transporters (GATs)
- GABA is enzymatically modified by GABA- transaminase to succinate semialdehyde in glial cell
What are 2 mechanisms of neurotransmitter inactivation?
° Reuptake into pre-synaptic terminal to be reused
° Enzymatic degradation in the synaptic cleft
How can normal brain activity be described?
Non-synchronous
How can brain electrical activity be described during seizures?
group of neurones begin firing in an abnormal, excessive, + synchronised manner, resulting in a wave of depolarisation.
What causes the wave of depolarisation in seizures?
• influx of Ca2+ from outside of the cell → extended opening of Na+ channels + repetitive action potentials.
→ hyperpolarisation facilitated by γ-aminobutyric acid (GABA) receptors or potassium (K+) channels, depending on the type of cell.
What is abnormal cell firing in seizures associated with?
Excess glutamate in the synapse
What can excess glutamate in synapses cause physically?
Convulsions
What machine can be used to measure brain electrical activity?
Electroencephalography (EEG)
What drugs facilitate GABA transmission?
- Anti-epileptic
- Anxiolytic
- Sedative
- Muscle relaxants
