lecture 7 - redone Flashcards
what is CFTR
an anion channel that controls the amount of epithelial secretions (e.g ASL)
what is the most common mutation
f508del
what is class 1 mutation
G542X - no protein
what does the X is G542X represent
a stop mutation
class II mutation
f508del - no traffic
why does class II mutation not processed to the membrane
as the protein is misfolded
class III mutation
G551D - no function
what does the no function mutation cause
the channel doesn’t respond to normal queues that activates it (gating mutation)
class IV mutation
R117H - less function
cant conduct chloride and bicarbonate as well as the wild type
class V mutation
A455E - less protein
class VI mutation
rF508del - less stable
class VI mutation has a shorter half life because
it gets retrieved from the membrane earlier
other factors that affect lung disease
- single nucleotide polymorphisms (SNPs)
- air pollution
SNPs
alter the activity and function of other genes which can modify the disease severity
ASL is made up of
mucus layer and periciliary liquid layer
what is the periciliary liquid layer
cilia in the salty solution
proper hydration ensures efficient mucociliary clearance (MCC) which removes
pathogens
in a healthy cell if theres too much fluid in ASL
ENaC is activated
in a healthy cell if there isnt enough fluid in the ASL
CFTR is activated
CFTR has a negative effect on ENaC so without CFTR, ENaC is
overactive, making dehydration worse
in CF the pH of ASL is
more acidic
consequences of more acidic pH
- increases ENaC activity
- decreased bacterial killing
- increased mucus viscosity
how does acidic pH increase ENaC activity
increase CAP and decrease SPLUNC1 function
how does acidic pH increase mucus viscosity
conformational changes in the mucins making them more rigid
