Respiratory Channelopathies

Question 1

How is cystic fibrosis inherited

Answer 1

autosomal recessive

Question 2

What tissue does cystic fibrosis impact

Answer 2

epithelial tissue

Question 3

What channels does cystic fibrosis affect

Answer 3

chloride ion transport channels

Question 4

What is cystic fibrosis a disease of

Answer 4

electrolyte transport

Question 5

Where is the main impact of cystic fibrosis

Answer 5

airways

Question 6

What is the most common symptom of cystic fibrosis

Answer 6

BLOCKAGE

Question 7

What is a good marker for cystic fibrosis

Answer 7

salty sweat

Question 8

Do carriers for cystic fibrosis exhibit symptoms

Answer 8

NO

Question 9

What gene is mutated in cystic fibrosis

Answer 9

Cf gene

Question 10

What does the Cf gene code for

Answer 10

cystic fibrosis transmembrane conductance regulator

Question 11

How many transmembrane spanning domains does the CFTR channel have

Answer 11

12

Question 12

Where does the regulatory domain of the CFTR channel sit

Answer 12

intracellularly

Question 13

What is located on the structure of the CFTR channel

Answer 13

2 nucleotide binding domains, regulatory domain

Question 14

What is the importance of the nucleotide binding domains on CFTR

Answer 14

important for function

Question 15

Why are the nucleotide domains important for function

Answer 15

bind to ATP which regulates function

Question 16

What is the most common mutation for cystic fibrosis

Answer 16

F508 - deletion mutation

Question 17

Describe the effect of class I mutations in cystic fibrosis

Answer 17

null production due to unstable mRNA

Question 18

Describe the effect of Class IV mutations in cystic fibrosis

Answer 18

conduction issue

Question 19

Describe the effect of Class III mutations in cystic fibrosis

Answer 19

Regulation issue

Question 20

Describe the effect of Class VI mutations in cystic fibrosis

Answer 20

High turnover of CFTR

Question 21

Describe the effect of Class II mutations in cystic fibrosis

Answer 21

trafficking issues

Question 22

Describe the effect of Class V mutations in cystic fibrosis

Answer 22

partial reduction in mRNA

Question 23

What are the effects of cystic fibrosis on the lungs

Answer 23

Mucous cant be cleared easily, bacterial infections are frequent

Question 24

What happens when cystic fibrosis patients have severe lung infections

Answer 24

inflammation, tissue degeneration

Question 25

Describe the intracellular chloride concentration

Answer 25

high

Question 26

Which membrane does CFTR sit on

Answer 26

apical

Question 27

What does CFTR inhibit normally

Answer 27

ENaC

Question 28

What is the effect of a CFTR mutation on ENaC

Answer 28

ENaC function increases

Question 29

What is the effect of increased ENaC function

Answer 29

increased sodium absorption, sodium and water move into the cell

Question 30

What happens when water is lost from the liquid layer on the apical membrane in the lungs

Answer 30

cilia bend, lose function, infections occur

Question 31

Why is it thought that cystic fibrosis have a high prevalence in the population

Answer 31

protection against cholera

Question 32

What are mucolytics

Answer 32

enzymatic drugs, break down mucous

Question 33

What are the current treatments for cystic fibrosis

Answer 33

physio, bronchodilators, antibiotic steroids, mucolytics

Question 34

What are the disadvantages of gene therapy as a treatment

Answer 34

challenging, poor success rate, expensive

Question 35

Describe how gene therapy would work for cystic fibrosis

Answer 35

delivery of CFTR DNA to target cells, DNA transcribed into mRNA -> protein

Question 36

What is a new approach for cystic fibrosis treatment

Answer 36

small molecule treatments

Question 37

How do corrector treatments for cystic fibrosis work

Answer 37

force mutant CFTR proteins to the membrane

Question 38

How do potentiator treatments work to treat cystic fibrosis

Answer 38

increase the open probability of CFTR channels

Question 39

Example of a potentiator

Answer 39

Ivacaftor

Question 40

When patients with cystic fibrosis were treated with Ivacaftor what was the effect on their symptoms

Answer 40

NO symptoms exhibited