Epithelial Chloride Channels 1 Flashcards
Functions of fluid secretion
digestion, reabsorption
washes away injurious substances
mixes nutrients and enzymes
present nutrients to absorptive surface
Fluid along GI tract
+1L, +2L stomach, +1.5L small intestine, +1.5L pancreas
-6.5L small intestine
-1.3L large intestine
excrete 0.2L
secretory diarrhoea
eg vibrio cholerae, E coli
up to 25L a day
Alot or no fluid secretion in CF?
little or none
mucus in CF
mucus overlying epithelium becomes dehydrated, sticky and impenetrable
problems with CF
malnutrition
intestinal blockage
bacterial infection of airways
crypts and villi
villi absorb and crypts excrete
T84 cells
secrete chloride ions
grew on permeable support - formed microvilli
T84 cell + chamber
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
short circuit current
measure of chloride ions across partition
current when voltage is 0
who comprised mechanism for chloride trasnport?
dhamsathaporn 1980s
chloride transport with Na/KATPase
Na/KATPase
K leaks out
2 chlorides in - balance charge
water paracellular
what 2 pathways involved in chloride trasnport?
calcium and cAMP
Oubain
blocks chloride secretion from basolateral side
inhibits Na/KATPase
loop diuretics - examples and how they work
furosemide
inhibit Cl secretion
basolateral side
experiment - 2Cl for 1 Na and 1K
radio-isotope studies: 22Na, 36Cl, 86Rb (K)
Oubain present - loop diuretics flux of Na, Cl or K requires presence of other 2
Dhamsathaporn 1986 - bumetanide and Isc
Isc - high in control after 0.1mM carbachol (activates AchR)
Isc unaffected with bumetanide - chloride secretion blocked
what is VIP? What does it do to chloride and K secretion?
intestinal polypeptide - vasoactive
increased Cl and K secretion
K secretion <5% Cl
what happens if K not recycled across basolateral membrane?
cell depolarises
86Rb basolateral vs apical efflux
in control condition basolateral 10-100x greater
VIP on K efflux
increases basolateral
no effect on apical
What does basolateral barium do? how does it work?
blocks chloride secretion
block K channels
Barium and VIP experiment
both work on potassium channels
VIP increase basolateral efflux
barium blocks this
how many chloride channels identified in T84 cells? activated by what?
3
cAMP, calcium and volume/swelling
of the 3 chloride channels which is CFTR activated by?
Cystic Fibrosis Transmembrane conductance Regulator
cAMP
responsible for CF and choleria
