Flashcards in Chemical Signalling Deck (11):
How does Synaptic transmission work?
Action potential reaches the synaptic terminal. Neurotransmitters are released and diffuse across the synaptic cleft. Receptors recognize the neurotransmitters and initiate a response
1) Direct excitatory or inhibitory neurotransmission
i.e. the next cell fires an action potential or is inhibited
alter the presynaptic cell’s ability to release more transmitter or the postsynaptic cells ability to respond
Categories of neurotransmitter
(e.g. GABA, glutamate) - responsible for fast transission
(e.g. Dopamine, serotonin)
Glutamate synthesis, storage, release and reuptake
1) synthesized in nerve terminals from
glucose or glutamine
2) loaded and stored in vesicles by
vesicular glutamate transporters
3) released by exocytosis (Ca2+ dependent mechanism)
4) acts at Glutamate receptors on postsynaptic membrane
5) Reuptake by excitatory amino acid transporters (EAATs) in the plasma membrane of presynaptic cell and surrounding glia
What happens if there is too much glutamate or too little GABA?
hyperexcitability – epilepsy (caused by stroke, infection, trauma)
What is Cerebral ischemia?
(insufficient blood flow due to plaque, tumor) Symptoms: weakness, visual impairments
Action of neurotransmitters at receptors: Pharmacology?
Agonist - a drug (or endogenous ligand/neurotransmitter) that can combine with a receptor on a cell to produce a cellular reaction
Antagonist – a drug that reduces or completely blocks the activity of the agonist or endogenous ligand, no cellular effect after interacting with receptor
Which ionotropic receptor have been described that respond to glutamate?
NMDA, AMPA and Kainate
NMDA receptors and Schizophrenia?
NMDA receptors also blocked by phencyclidine (PCP, angel dust) and MK801 which both bind in the open pore.
Blockade of NMDA receptors in this way produces symptoms that resemble the hallucinations associated with Schizophrenia (associated with reduced NMDAR function).
Certain antipsychotic drugs enhance current flow through NMDA channels
GABA synthesis, storage, release and reuptake
1) GABA is synthesized from glutamate
2) GABA is loaded and stored into
synapses by a vesicular GABA
3) GABA released by exocytosis (Ca2+ dependant mechanism)
4) GABA acts at ionotropic GABAA and metabotropic GABAB receptors on postsynaptic membrane
5) GABA cleared from synapse by reuptake using transporters on glia and neurons including non-GABAergic neurons
more dangerous - too much can block your breathing.
difference between therapeutic dose and dangerous dose is so small. can lead to depression and can lead to suicide. now its only used to treat seizures and to treat people with insomnia