Epithelial Chloride Channels 2 Flashcards
CF information
1 in 2500 caucasian births
dysfunctional wet epithelium
block pancreatic ductules
inability to clear mucus
diagnosing CF
CF sweat 3-5 times more NaCl
sweat duct normal
NaCl in sweat gland and reabsorbed higher up
water onto skin surface
Paul Quinton 1983 - name of paper
chloride impermeability in CF
Paul Quinton 1983 findings
potential difference across CF sweat duct epithelial higher than normal
PNa/PCl 10 fold higher
reduced Cl permeability accounts for CF symptoms
non cf vs cf sweat duct epithelium
apical –> basolateral membrane
absorption of chloride and sodium
excrete chloride, Na via Na/K ATPase
apical Cl disturbed, not reabsorbed
Michael J Welsh 1986
Apical membrane Chloride channel in human tracheal epithelium
What did Michael J Welsh do in 1986?
patch clamp study of apical Cl channels in tracheal epithelium
ORCC
outward and inwards current movement of ions
outward = move in
inward = move out
direction +ve charge moves
Who first identified ORCCS?
MIchael J Welsh
What is a symmetrical channel?
ions move in both directions
I/V proportional
epithelial chloride channels - ORCCS
more current at positive voltages than at negative
positive inside - outward current
positive voltages and more current
let more chloride from outside to inside
airway - trying to find channel let chloride out of cell
Frizzell 1986 - other paper which came out similar?
Altered regulation of airway epithelial cell chloride channel in CF
Chloride and potassium channels in CF airway
Frizzel and Welsh 1986 findings
failure of beta adrenergic agonists to activate ORCCs in CF airway
1987 Schoumacher
phosphorylation fails to activate chloride channels in CF airway
Schoumacher 1987 findings
failure of PKA to activate ORCCS in CF airway epithlial cells
ORCCS were present in CF and activated by strong depolarisation
1988 Li
cAMP dependent PKA open Cl channels in normal but not CF airway epithelium
LI 1989
Regulation of chloride channels by PKC in normal and CF epithelium
findings from Li 1989
failure of PKA activate ORCCS in CF - defect of channel or regulatory protein
PKC activated ORCCS in normal but not CF
defective transduction from phosphorylation sites to channel gating mechanism
1989 Gray
2 types of Cl channel on duct cells from human fetal pancreas
who found SLCC?
gray et al in 1989
2 types of chloride channels
SLCC in apical membrane of pancreatic duct cells
ORCCS infrequently
what activated SLCC?
secretin and cAMP
conductance of SLCC
small and linear
