Cl channel and CFTR

Question 1

voltage gated Cl- channel

Answer 1

Double barrel shotgun with a double lock
2 independently gated pore, there is also a common slow gate: it is a homodimer but the 2 subunits form and indiviual pore

Stabilised by helix dipoles

Question 2

Human CLc proteins

Answer 2

Clc 1:

location: smooth muscle
role: stabilises resting membrane potential
mutation: unstable resting membrane potential, hyperactive muscle fiber (myotonia)

Clc5:

location: kidney, proximal tubule
role: Cl- transport
mutation: hypercalcinuria, nephrolithiasis

ClKa-Kb

location: kidney, TAL of loop of henle
role: Cl- reabsorption
mutation: Kb, salt waste, polyuria

Question 3

CFTR

Answer 3

ATP binding cassette protein
2 TMD 2 NBD (most highly conserved module of ABC proteins) and one R-regulatory domain
48 human ABC proteins in total: TAP (antigen presenting), P-glycoprotein (multidrug resistance), SUR (K-ATPase)

Question 4

regulation of CFTR

Answer 4

ATP actiavte the channel by binding to the 2 NBD subunit
very high affinity
but physiological activator: PKA phosphorylate 10 serine residues in the R domain
the more you phsophorylate the higher the channel activity

Question 5

Gating cycle of CFTR

Answer 5

NBD1 and NBD2, heterodimers, with 2 ATP sandwiched btw them
open if NBD dinerized
closed when NBD2 ATP is hydrolysed -y dimer dissociates, pore closes

Question 6

Cystic fibrosis or Mucovicidosis

Answer 6

1. autosomal recessive
2. defect of pretein folding/processing
3. gating or permeation defect
   Symptoms
   muscous viscous (lung infections)
   pancreatic insufficiencies
   high salt sweat
   meconium ileus