L21- GABA and Dopamine Flashcards
Major inhibitory neurotransmitter of the nervous system
GABA
GABA activation at neurons causes _______
hyperpolarization
how is GABA synthesised
what are the two classifications of GABA receptors
Ionotropic and Metabotropic
function of GABAa + c receptors
opens chloride channels causing a influx of negative charge into the cell causing hyperpolarisation
function of GABAb receptors
indirectly opens potassium or calcium channels via g proteins causing the release of positive charge from the neuron causing hyperpolarization
activation of GABAa receptors in the synapse
causes rapid inhibition and return to steady state
activation of extra synaptic GABAa receptors
excess release of GABA presynaptically (spill over) causes tonic inhibition
GABAc receptors expression
in the retina and axonally on bipolar
cells
what is the suggested role of GABAc function
may have a role in myopia, pain and some neurological disorders
Side effects of GABAc modification
GABAc receptors are relatively sparse in the body relative to other GABA receptor types
modification of these receptors has limited systematic side effects
where are GABAb receptors located
glial cells
pre and post-synaptic neurons
activation of PRE-synaptic GABAb receptors
Inhibit the presynaptic neuron and the calcium dependent neurotransmitter release (auto-reception)
activation of POST-synaptic GABAb receptors
receptors activate potassium channels and lead to a slow hyperpolarisation
How many GAT subtypes are there
4
location of GAT 1
mainly located on presynaptic terminals, axon initial segments and glial cells
location of GAT 2/3
mainly located on glial cells
how is GAT transport mediated
secondary active transport
- Co transport 2 sodium, 1 chloride with 1 GABA
role dopamine in the CNS
modulated excitation and inhibition depending on location
Has a diverse role in the nervous system:
* Movement
* Reward
* Motivation
how many dopamine subtypes are there
5- D1-5
how many dopamine classes are there
2 - D1&2
Function and location of D1 class
D1 class activate Gαs/olf to stimulate cAMP production by adenylyl cyclase
- increasing PIP2 hydrolysis
- Ca+ mobilization
- PKC activation
location of D1 class
only found post-synaptically
Function and location of D2 class
activate G αi/o to inhibit adenylyl cyclase
- decreases cAMP
- increases K+ currents
- decreases Ca+ currents
location of D2 class
pre and post synaptically
activation of PRE-synaptic D2 class receptors
Low amounts of dopamine activate D2 receptors
causes negative feedback (auto-reception)
bi phasic response of DA receptors
D2 presynaptic neuron are activated by lower levels of dopamine then post synpatic neurons
how is negative feedback mediated at the presynaptic neuron
Ca+ channel that are needed to release vesicles of neurotransmitters into the synapse are blocked
K+ channels are opened hyperpolarizing the cell
L-DOPA
L-DOPA is the DA precursor and indirect agonist for DA receptors
Used for dopamine replacement therapy
Many uses for antipsychotic outcomes
DAT function
Returns DA to the presynaptic terminals via secondary active transport (reuptake)
Cotransports 2 sodium, 1 chloride into the cell along with 1 dopamine
pharmacological relevance of DAT
blocking (cociane) or reversing DAT (amphetamine) pump dopamine into the synapse
monoamine oxidase inhibitors
MAOs are enzymes that break down monoamines - inhibiting this process maintains the effects of dopamine
TRUE or FALSE: neurons release only one kind of neurotransmitters
FALSE: Neurons in the olfactory bulb
release both GABA and DA
