INHIBITORY TRANSMISSION Flashcards
GABA influences neuronal signalling via activation of what
GABAa and GABAb receptors
The major inhibitory receptor in the mammalian brain is what
GABAa receptor
In the spinal cord fast inhibition is mediated by what
GABAaRs and glycine receptors
GABAaR inhibitors are what
proconvulsant and anxiogenic
Drugs that enhance GABAaR functions are called what
Positive allosteric modulators- PAMs (diazepam)
They are anticonvulsant, anxiolytic, sedative and analgesic
Describe the structure of GABAbR
A heterodimer with GABAB1 providing the GABA binding domain and GABAB2 the G protein coupling to Gai and Gao
What is Baclofen
A skeletal muscle relaxant acting on the spinal cord
A seelctive GABABR angonist used clinically to treat certain types of spasticity (muscle stiffness) resultant from multiple sceloris and spinal cord injuries
What is GABA-T
Gaba-transaminase
Describe the process of inhibitory GABA-ergic transmission
a-ketoglutarate works with GABA-T to turn into glutamate where then GAD (Glutamic acid decarboxylase) turns this into GABA
This GABA then goes through endocytosis and is pacled into vesicles where it goes through exocytosis and exits the synapse through to the GABAaR receptor
What is phasic inhibition
Phasic inhibition is mediated by the fast activation of synaptic GABAARs from synaptically released GABA
What is tonic inhibition
Tonic inhibition depends on the sustained activation of peri- and extrasynaptic GABAARs by ambient GABA in the extracellular space.
What is feed forward inhibition
Involves a bi-synaptic inhibitory response. GABA arrives only 1-5msec after the monosynaptic excitory glutamate input, therby inhibiting the time window for summation of excitory inputs to generate an action potential
Activation of glutamate-gated cation conducting channels produce an excitory postsynaptic potential (EPSP)
Activation of GABA- gated anion conducting channels produce an inhibitory postsynaptic potential (IPSP)
What is feedback inihibition
The firing of the pyramidal neuron activates an inhibitory interneuron, which in turn inhibits the pyramidal neuron. once the inhibition decays, the pyramidal neuron can fire again
What does the Gi alpha subunit inhibit
adenylate cyclase activity to decrease cAMP levels
Post synaptic GABAb activation causes the Gi beta gamma complex to open what?
Open the K+ channel causing hyperpolarisation