Respiratory Channelopathies Flashcards
How is cystic fibrosis inherited
autosomal recessive
What tissue does cystic fibrosis impact
epithelial tissue
What channels does cystic fibrosis affect
chloride ion transport channels
What is cystic fibrosis a disease of
electrolyte transport
Where is the main impact of cystic fibrosis
airways
What is the most common symptom of cystic fibrosis
BLOCKAGE
What is a good marker for cystic fibrosis
salty sweat
Do carriers for cystic fibrosis exhibit symptoms
NO
What gene is mutated in cystic fibrosis
Cf gene
What does the Cf gene code for
cystic fibrosis transmembrane conductance regulator
How many transmembrane spanning domains does the CFTR channel have
12
Where does the regulatory domain of the CFTR channel sit
intracellularly
What is located on the structure of the CFTR channel
2 nucleotide binding domains, regulatory domain
What is the importance of the nucleotide binding domains on CFTR
important for function
Why are the nucleotide domains important for function
bind to ATP which regulates function
What is the most common mutation for cystic fibrosis
F508 - deletion mutation
Describe the effect of class I mutations in cystic fibrosis
null production due to unstable mRNA
Describe the effect of Class IV mutations in cystic fibrosis
conduction issue
Describe the effect of Class III mutations in cystic fibrosis
Regulation issue
Describe the effect of Class VI mutations in cystic fibrosis
High turnover of CFTR
Describe the effect of Class II mutations in cystic fibrosis
trafficking issues
Describe the effect of Class V mutations in cystic fibrosis
partial reduction in mRNA
What are the effects of cystic fibrosis on the lungs
Mucous cant be cleared easily, bacterial infections are frequent
What happens when cystic fibrosis patients have severe lung infections
inflammation, tissue degeneration
Describe the intracellular chloride concentration
high
Which membrane does CFTR sit on
apical
What does CFTR inhibit normally
ENaC
What is the effect of a CFTR mutation on ENaC
ENaC function increases
What is the effect of increased ENaC function
increased sodium absorption, sodium and water move into the cell
What happens when water is lost from the liquid layer on the apical membrane in the lungs
cilia bend, lose function, infections occur
Why is it thought that cystic fibrosis have a high prevalence in the population
protection against cholera
What are mucolytics
enzymatic drugs, break down mucous
What are the current treatments for cystic fibrosis
physio, bronchodilators, antibiotic steroids, mucolytics
What are the disadvantages of gene therapy as a treatment
challenging, poor success rate, expensive
Describe how gene therapy would work for cystic fibrosis
delivery of CFTR DNA to target cells, DNA transcribed into mRNA -> protein
What is a new approach for cystic fibrosis treatment
small molecule treatments
How do corrector treatments for cystic fibrosis work
force mutant CFTR proteins to the membrane
How do potentiator treatments work to treat cystic fibrosis
increase the open probability of CFTR channels
Example of a potentiator
Ivacaftor
When patients with cystic fibrosis were treated with Ivacaftor what was the effect on their symptoms
NO symptoms exhibited
