DJW

Question 1

Which residue(s) is responsible for single channel conductance? Why is the position of those residue control conductance?

Answer 1

Ser/Leu residue in M3 region

Because they’re thought to control the conformation of the open pore

Question 2

Residues that are involved in glycine potency

1. GluN2A
2. GluN2B

Answer 2

1. Y735 K719

2. K756 M740

Question 3

Describe the action of NKCC1 and KKC2 and their relative expression throughout development

Answer 3

NKCC1: transport Cl from extra to intra
- higher expression in immature neurons

KKC2: transport Cl- from intra to extra
- expression largely increase throughout development

Question 4

Name the diseases associated with abnormal expression of chloride transporter

Answer 4

Fragile X Syndrome
Rett’s syndrome
Schizophrenia

Question 5

Where in the CNS is delta subunit mostly express?

Answer 5

Granule cells of the cerebellum

Question 6

Which subunit and residue is critical for the action of BDZ?

Answer 6

Alpha 1,2,3 and 5

Histidine residue

Question 7

ADNFLE

• which receptor is mutated?
• name the mutated amino acid and in which region?
• what properties of the channel is affected?

Answer 7

• neuronal nicotinic alpha-4 subunit
• S247F in M2 region
• net charge flowing greatly reduced
• EC50 higher in mutant
• rightward shift of dose-response curve
• decrease slope - gating mutation
• decrease permeability to calcium —> impaired transmitter release
• reduce in open time
• reduce conductance

Question 8

Which sort of de novo mutation is memantine use for? Describe the properties of this mutation

Answer 8

Memantine is an NMDA use-dependent blockers

Leucine mutation in pre M4 region

• leucine has a critical role in gating of channel by interactions with pre M4 region
• GOF mutation
• increase glycine potency
• increase open time
• prolong depolarisation hence EPSP
• DEACTIVATION slower

Question 9

Myasthenia

Answer 9

• Rapidly decaying and low EPPs amplitude
• single channel currents - reduce
• briefer events - no sufficient depolarisation
• mutation in cys-loop region LBS critical for binding
• dissociation rate constant greatly increase
• Ach dissociate much more rapidly - shorter bursts length
• not enough Ach at cleft to overcome large dissociation rate