Lecture 2 - ASL, influenza and ion channels

Question 1

Pericilliary layer

Answer 1

sits on top of cells with cilia projecting from cells which beat to move liquid up the tract

Question 2

Roles of airway surface liquid (2)

Answer 2

mucus clearance and first line of defence against infection

Question 3

Moving up the airway tract … which means….

Answer 3

small airways converge in the bronchial region so surface area increases and this changes volume

Question 4

Changes in volume load means….

Answer 4

mechanisms are needed to regulate ASL height to ensure it is optimum

Question 5

Describe passive ASL control

Answer 5

mucus layer acts as a reservoir, so excess fluid enters or leaves layer depending on requirements

Question 6

Describe active ASL control

Answer 6

active ion transport to control PCL salt levels

Question 7

Optimum ASL height

Answer 7

~7.5cm2

Question 8

Describe what occurs at high ASL heights

Answer 8

ENaC dominates to increase sodium absorption, water follows therefore ASL height decreases
Cl- secretion at low levels

Question 9

Describe what happens to ASL at steady states

Answer 9

CFTR dominates for chloride secretion to maintain ASL height

no net movement

Question 10

describe Bumetanide in dominating experiments

Answer 10

NKCC1 blocker to block chlorine secretion

used to show CFTR contribution to height

Question 11

Describe amiloride in dominating experiments

Answer 11

ENaC blocker to prevent sodium reabsorption to show ENaC contribution to height

Question 12

Water movement in cells

Answer 12

balance between Cl- secretion and sodium reabsorption

transport is paracellular

Question 13

10% hospital admissions during flu season are due to (2)….

Answer 13

influenza linked bronchopneumonia and oedema, or acquired respiratory distress syndrome

Question 14

Murine nasa PDS

Answer 14

used to measure transepithelial potential of the nasal epithelium

Question 15

murine nasal PDS in normal cells

Answer 15

amiloride added = shifts potential to show ENaC function
adding Forskolin and GlyH-101 = show CFTR function
bigger shift=bigger function

Question 16

Influenza murine nasal PDS shows…

Answer 16

by day 5 ENaC is inhibited but recovers by day 15

CFTR is inhibited days 5-15

Question 17

CFTR in influenza

Answer 17

sustained inhibition

Question 18

ENaC in influenza

Answer 18

transient inhibition, recovers by day 15

Question 19

HBR monolayers Ussing data

Answer 19

reduced ENaC and CFTR function
shifts very small in infected cells
infection effects channel no. or Po

Question 20

Patch clamping results

Answer 20

infected cells show a reduced Po of ENac and CFTR

Question 21

ASL in influenza

Answer 21

ASL has a sustained reduction in infected cells, so cilia function is also reduced

Question 22

Lumacaftor

Answer 22

CFTR corrector to traffic CFTR to the membrane which helps to increase ASL height

Question 23

Lumacaftor and influenza

Answer 23

helps increase ASL height but not to control levels, so may be used to treat patients with influenza without CF