central neurotransmitters Flashcards
Synaptic Transmission
4 steps for synpatic transmission?
- An action potential arrives at the synaptic bouton
- Voltage gated calcium channels open
- ↑[Ca2+]i initiates vesicle fusion with the presynaptic membrane
- Neurotransmitter is released into the synapse, where it interacts with receptors
Synaptic receptors (2)
Ionotropic and metabotropic
Ionotropic receptors
type
speed
Ligand-gated ion channels
FAST synaptic transmission
Metabotrophic
type
speed
GPCRs - G-protein coupled receptors (mostly)
SLOW signal modulation
Synaptic termination
cleared by? (3)
- Neurotransmitter is cleared from the synapse
i. Enzymatic breakdown
ii. Re-uptake into
presynaptic terminal
iii. Diffusion away from
synapse
overview of ap and propagation
how do ap travel?
why is signal transduction fast?
myelin sheaths in pns?cns?
rmp? what is allowed to move out of the cell? what happens with depolarisation? what happens at peak of positivity? how hyperolarised? what returns its back to rmp? what happens when ap gets to synaptic bouton? effect? (2) what is released?
• APs travel along an axon by jumping from node to node
• these nodes have many voltage gated Na+ and K+ channels which open and close as AP
propagates
• Signal transduction is very fast due to the insulation by myelin sheaths
• oligodendrocytes make up myelin sheaths in the CNS
• in the PNS, myelin sheaths are made by schwann cells
• A nerve cell is constantly at a resting membrane potential of -70mV
• K+ membrane channels allow K+ to move outside the cell making the inside of the cell
negative at a PD of -70mV
• as the cell is depolarized, Na+ voltage gated channels open and there is an influx of Na+
making the cell +ve
• at the peak of the positivity, voltage gated K+ channels open and K+ ions leave the cell thus
making the cell -ve in the inside
• excess of K+ exits the cell making it hyperpolarized
• Na+/K+ ATPase pumps then return the cell back to RMP
• At the synaptic bouton, the depolarization leads to
opening of voltage gated Ca2+ channels
• there is an influx of Ca2+ in to the cells
• this leads to an effective release of neurotransmitter
from the presynaptic membrane
• the NT vesicle gets signaled to fuse with the
presynaptic membrane, and release its contents
through exocytosis (neurotransmitter)
• the NT is released into the synapse where it acts on
receptors
• a protein called clathrin binds to the cell membrane
turning it into an endocytotic membrane thus allowing
reuse and recycling of neurotransmitter
Glutamate transmission and termination at synaptic cleft
amino acid transmitter
what converts what to glutamate? how does this enter vesicles?
what is eaat? where does this go? (2)
where are GinT transporters?
Glutaminase converts glutamine to glutamate which gets into vesicles via vGlut channels
Upon AP/activation, glutamate is released in synaptic cleft where it will act on glutamate receptors
EAAT is a glutamate transporter therefore will re-uptake either into neuron where it will be recycled into vesicles OR via an astrocyte it will be converted via glutamine synthase into glutamine and transported back into neuron via GinT transporter.
Why is too much glutamate bad?
can lead to hyper excitability hence cause exocytoxicity and eventually lead to cell death
effect of NMDA antagonist (4)
can be used to treat : glutamate exitotoxicity epilepsy stroke depression
Hypofunction of NMDA
can lead to schitzophrenia
summary of gluatamate
what is it?
receptors abundant where?
what are the 4 receptor subtypes?
NMDA receptors - 2 roles?
NMDA antagonists - 3 reasons
AMPA modulators (AMPAkines)/colocalisation with NMDA - why?
Main excitatory transmitter
Receptors abundant in cortex, basal ganglia, sensory pathways
Four main receptor subtypes
NMDA, AMPA & Kainate (ionotropic) Q. fast or slow?
Metabotropic (G-protein coupled) / modulatory 8 subtypes
(antagonists: potential for PD, addiction, epipepsy)
NMDA receptors (pre- and post synaptic)
Role in synaptic plasticity (hippocampus)
Role in memory, stroke
NMDA antagonists
Epilepsy (lamotrigine)
Stroke – neuronal damage caused by excess glutamate
Schizophrenia, drug abuse
AMPA modulators (AMPAkines)/colocalisation with NMDA Cognitive enhancement
Glutamate/NMDA/glycine
NMDA colocalised with AMPA receptors. Highly permeable to Ca2+ but at resting potential channel blocked with Mg2+, only when cell is depolarised (e.g. activation of AMPA receptor) Mg2+ moves out and allows Ca2+ to flow in. Also needs glycine to bind (glycine thought of as an inhibitory transmitter) therefore glycine antagonists can inhibit glutamate action. Some anaesthetics (ketamine) and psychotomimetics (phencyclidine) block the NMDA channel. Glycine site may be important as may have fewer side effects – results from clinical trials so far have not been conclusive
what is GABA?
speed?
what does it do? where?
highest density where?
Y-aminobutyric acid (GABA) Amino acid transmitter Main inhibitory transmitter in CNS (fast transmitter) Mostly via inhibitory interneurons Highest density in nigrostriatal system
which conditions is GABA important for? (2)
anxiety and insomnia due to reduced GABA
How is GABA synthesised and deactivated?
synthesised from? via?
deactivated - (2)
GABA synthesised from glutamate
Glutamic acid decarboxylase GAD
Deactivation
Re-upatake via GABA receptor
GABA transaminase (GABA-T) will break it down once in neuron/astrocyte
Drug to increase GABA (2)
GABA transaminase inhibitor
GABA reuptake inhibitor
GABAa and GABAb
GABAa receptor? speed? increase this effect? drug that open this channel (2) inhibit GABA transaminase drug?
GABAb receptor? effect?
GABAA receptor – ligand gated Cl- channel
Fast postsynaptic inhibition
Drugs that ncrease GABA or activate of GABAA receptors are used for management of epilepsy (antiepileptic)
Benzodiazepines, barbiturates – facilitate channel opening
Vigabatrin – inhibits GABA transaminase
GABAB receptor (dimer) – G-protein coupled (inhibit Ca++, AC, open K+, inhibit NT release)
Baclofen GABAB activation (inhibit glut, opioid, GABA release)
Baclofen – antispastic effect, drug addiction? (alchohol)
g hydroxybutyrate (GHB): partial agonist of GABAb
What condtions do BZD treat? (4)
treat seizures, anxiety, insomnia and epilepsy
