Epithelial Chloride Channels 1

Question 1

Functions of fluid secretion

Answer 1

digestion, reabsorption
washes away injurious substances
mixes nutrients and enzymes
present nutrients to absorptive surface

Question 2

Fluid along GI tract

Answer 2

+1L, +2L stomach, +1.5L small intestine, +1.5L pancreas
-6.5L small intestine
-1.3L large intestine
excrete 0.2L

Question 3

secretory diarrhoea

Answer 3

eg vibrio cholerae, E coli

up to 25L a day

Question 4

Alot or no fluid secretion in CF?

Answer 4

little or none

Question 5

mucus in CF

Answer 5

mucus overlying epithelium becomes dehydrated, sticky and impenetrable

Question 6

problems with CF

Answer 6

malnutrition
intestinal blockage
bacterial infection of airways

Question 7

crypts and villi

Answer 7

villi absorb and crypts excrete

Question 8

T84 cells

Answer 8

secrete chloride ions

grew on permeable support - formed microvilli

Question 9

T84 cell + chamber

Answer 9

cells take chloride channels from inside and move outside
negative charge across epithelium
potential difference
pass current in opposite direction until voltage at 0
current = chloride secretion

Question 10

short circuit current

Answer 10

measure of chloride ions across partition

current when voltage is 0

Question 11

who comprised mechanism for chloride trasnport?

Answer 11

dhamsathaporn 1980s

Question 12

chloride transport with Na/KATPase

Answer 12

Na/KATPase
K leaks out
2 chlorides in - balance charge
water paracellular

Question 13

what 2 pathways involved in chloride trasnport?

Answer 13

calcium and cAMP

Question 14

Oubain

Answer 14

blocks chloride secretion from basolateral side

inhibits Na/KATPase

Question 15

loop diuretics - examples and how they work

Answer 15

furosemide
inhibit Cl secretion
basolateral side

Question 16

experiment - 2Cl for 1 Na and 1K

Answer 16

radio-isotope studies: 22Na, 36Cl, 86Rb (K)

Oubain present - loop diuretics flux of Na, Cl or K requires presence of other 2

Question 17

Dhamsathaporn 1986 - bumetanide and Isc

Answer 17

Isc - high in control after 0.1mM carbachol (activates AchR)

Isc unaffected with bumetanide - chloride secretion blocked

Question 18

what is VIP? What does it do to chloride and K secretion?

Answer 18

intestinal polypeptide - vasoactive
increased Cl and K secretion
K secretion <5% Cl

Question 19

what happens if K not recycled across basolateral membrane?

Answer 19

cell depolarises

Question 20

86Rb basolateral vs apical efflux

Answer 20

in control condition basolateral 10-100x greater

Question 21

VIP on K efflux

Answer 21

increases basolateral

no effect on apical

Question 22

What does basolateral barium do? how does it work?

Answer 22

blocks chloride secretion

block K channels

Question 23

Barium and VIP experiment

Answer 23

both work on potassium channels
VIP increase basolateral efflux
barium blocks this

Question 24

how many chloride channels identified in T84 cells? activated by what?

Answer 24

3

cAMP, calcium and volume/swelling

Question 25

of the 3 chloride channels which is CFTR activated by?

Answer 25

Cystic Fibrosis Transmembrane conductance Regulator
cAMP
responsible for CF and choleria