L4 - Inhibition Flashcards
GABA reuptake
Via GAT, taken up by glial or taken back into nerve terminal and broken down into glucose -> glutamate -> GABA
Glycine reuptake
Via Glycine transporter, taken up by glial or taken back into nerve terminal (not broken down at all - compared to GABA which can be broken down)
GABA vs. Glycine
SIMILARITIES:
-Principal ion: Cl-
DIFFERENCES:
GABA is the predominant inhibitory NT forward of the medulla (CNS), it has both ionotropic and metabotropic classes
Where else Glycine is predominant in the spinal cord. It only has ionotropic receptor classes.
Glycine synthesis pathway
Glucose -> Serine -> Glycine
Produced from serine by action of Serine Transhydorxymethylase, which removes the carboxylic acid of the R group.
Most common GABA subunits
a1B2gamma2
What role do these play:
- Benzodiazepine
- Barbiturates
- Steroids
Benzo: modulate ability of recceptor to bind and transmit ions
Barbiturates: act as anaesthetic (potentiates function of receptor so its more active and clamps the neuron at a more hyperpol. state and hence is less likely to be activated/function.
What determines movement of an ion through an ion channel and the direction of that movement?
Drives exerted on ion channel (concentration and electrical gradient).
GOLDMAN EQN:
If PK = 1, then?
If PNa = 0, then?
Conclusion?
PK = 1 (The membrane represents no barrier to K+ movement)
PNa = 0 (the membrane is a perfect barrier to Na+ movement)
Conclusion: cell is only permeable to K+
The membrane potential Vm = -79.4 mV is for a cell perfectly permeable to K+ with the known intra and extra-cellular conc. Why then, do we always see the RMP of -65mV?
- > Not 100% permeable to K+
- > Some channels are closed
- > Leak from other channels e.g. Na+
Goldman Equation?
Determines reversal potential (also known as the Nernst potential). The reversal potential of an ion is the membrane potential at which there is no net (overall) flow of that particular ion from one side of the membrane to the other.
As cell develops, Cl- (intra) increases or decreases? What’s special about Cl- conc in the enteric NS?
Decreases. It is higher in the enteric NS.
What if we increase Cl - (intra)? What does this mean for GABA?
Vm increases (RMP increases), drive is going to be for the chloride to leave the cell to be closer to RMP so it depolarises.
This causes GABA to become excitatory instead of inhibitory as by opening the Cl- channels, allows Cl- to exit and depolarise. Hence GABA excited immature neurons and neurons of the enteric NS.
What is more important for an immature neuron?
Na+/K+/Cl- transporter or K+/Cl- transporter?
Na+/K+/Cl- transporter. K+/Cl- is more important for mature neuron.
GABA and Epilepsy - where are the mutations? What do they lead to? Whats special about the delta subunit?
- Mutation in gamma2 and alpha 1
- Mutations lead to a truncated receptor (Altered receptor kinetics, assembly, trafficking, cell surface expression and modulation by benzodiazepines and reduced GABA A receptor current).
- Mutations in delta subunit expressing GABA A R forms an extrasynapticc receptor which is though to play a role in tonic inhibition
G protein coupled receptor pathway
Molecule binds to receptor -amplified-> G proteins -> Adenylyl cyclase -amplified-> Clyclic AMP -> Protein Kinases -amplified-> Phosphates transferred to target proteins
