Neurotransmitters Flashcards
What is synaptic transmission?
Information transfer across the synapse requires release of neurotransmitters and their interaction with postsynaptic receptors •Rapid timescale •Diversity •Adaptability •Plasticity •Learning and memory
What is basic process of synaptic transmission?
- Transmitter released from 1st cell
- Synaptic activation of 2nd cell
- Signal integration and conduction by 2nd cell
- Signal transmitted to effectors or subsequent neurones
Electrical, chemical, electrical
What is the structure of a neurone?
Each neurone may receive and make several hundred or thousand synapses
Communication between cells requires neurotransmitter release
Describe neurotransmitters
- Enormous diversity in variety of transmitters and their receptors including Amino acids (e.g. glutamate, gamma amino butyric acid [GABA], glycine [gly]), amines (e.g. noradrenaline [NA] and dopamine [DA]) and neuropeptides (e.g. opioid peptides)
- Vary in abundance from mM to nM CNS tissue concentrations
- May mediate rapid (µs - ms) or slower effects (secs)
- Neurons receive multiple transmitter influences which are integrated to produce diverse functional responses
What are essential components for synaptic transmission?
- Restricted to synapses
- Calcium essential (transmitter release required increase in intracellular Ca2+ 200 micro M
- Transmission is fast - within ms molecules perSV
- Synaptic vesicles (SVs) provide het source of neurotransmitter (4,000-10,000 molecules per SV)
Summarise neurotransmitter release
Activation of transmitter release is calcium dependent and requires RAPID transduction 1. Membrane depolarisation 2. Ca2+ channels open 3. Ca2+ influx 4. Vesicle fusion 5. Vesicle exocytosis 6. Transmitter relase Electrochemical transduction from 2-8 200 mu secs
How to rapid release rates occur?
- Synaptic vesicles are filled with neurotransmitter (T) and disked in the synaptic zone
- Special proteins on the vesicle and pre-synaptic membrane enable fusion and exocytosis
Describe some neurotransmitters
- Vesicular proteins are targets for neurotoxins
- 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
Recap transmitter release requirements
- Calcium dependent (Ca2+)
- Transmitter-containing vesicles to be docked on the pre-synaptic membrane
- Protein complex formation between vesicle membrane and cytoplasmic proteins to enable both vesicle docking and a rapid response to Ca2+ entry leading to membrane fusion and exocytosis
- ATP and vesicle recycling
What is an ion channel receptor?
-fast response (msecs), medicate all fast excitatory and inhibitory transmission
CNS: Glutamate,
Gamma amino butyric acid (GABA)
NMJ: Acetylcholine (ACh) at nicotinic receptors
What is a G-protein coupled receptor?
slow response (secs/mins), Effectors may be enzymes (adenyl cyclase, phospholipase C, cGMP-PDE) or channels (e.g. Ca2+ or K+)
CNS and PNS: ACh at muscarinic receptors, dopamine (DA), noradrenaline (NA), serotonin (5HT) and neuropeptides (e.g. enkephalin)
Describe ion channel linked receptors
- Rapid activation µ to msec
- Rapid information flow Multiple subunit combinations-distinct functional properties
-Nicotinic cholinergic receptors (nAChR), glutamate (GluR), GABA (GABAR), Glycine (GlyR) receptors.
What is AMPA (glutamate receptor)?
- AMPA RECEPTORS
Alpha amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
Majority of FAST excitatory synapses
Rapid onset, offset and desensitisation
What is NMDA (glutamate receptor)?
- NMDA RECEPTORS
N-methyl-D aspartate
Slow component of excitatory transmission
Serve as coincidence detectors which underlie learning mechanisms
What happens in an excitatory CNS synapse?
- Glutamate synthesised from glucose via TCA cycle and transamination
- Glutamate reversibly bonds to post-synaptic receptors (linked to ion channels)
- Rapid uptake of glutamate by excitatory amino acid transporters (EAATs)
- Glutamate enzymatically modified by glutamine synthesise to glutamine synthesise in glutamine in gill cell