where is your rectal gland? karen hong warren pan chela brown ashish sharma brittany scarpato
Post on 14-Dec-2015
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Dogfish Shark (Squalus acanthias) rectal gland:a great model
• Purpose of the rectal gland• A single cell type--highly specialized for
transepithelial salt secretion• Holds the World Record for: Na/K ATPase activity,
Na/K/2Cl cotransporter activity (50x greater than mammalian kidney), and CFTR chloride channel activity
• One artery (usually), vein, duct--easy to cannulate and use for perfusion studies
• Model for hormonal regulation
K+Na+
BL SideApical Side
Na+
K+
2 Cl-
CFTRCl-
K+
-70mV
TAL vs the shark rectal glandAbsorption v. Secretion
K+Na+
BL SideApical Side
K+
Na+
K+
2 Cl-
Cl-
Barttin
ClC-Kb
Rectal Gland Cell Model
K+Na+
Basolateral SideApical Side
Na+
K+
2 Cl-
CFTRCl-
K+
cAMP
5’AMPC
ATP
PDE
K+
Rectal Gland Cell Model
K+Na+
Basolateral SideApical Side
Na+
K+
2 Cl-
CFTRCl-
K+ BaCl2 +
cAMP
5’AMPC
ATP
PDE
IBMX
Forskolin
K+
Bumetanide
Ouabain
Rectal Gland Cell Model
K+Na+
Basolateral SideApical Side
Na+
K+
2 Cl-
CFTRCl-
K+
K+
K+
K+
K+
K+
Cl-
Cl-
Cl-
-70mv
-15mv
Rectal Gland Cell Model
K+Na+
Basolateral SideApical Side
Na+
K+
2 Cl-
CFTRCl-
K+
K+
K+
K+
K+
K+
Cl-
Cl-
Cl-
Approaching -15mv
-15mv K+
K+
K+
K+K+
BaCl2 +
K+
K+
K+
K+
K+
K+
The Shark Rectal Gland: A Model Secretory Epithelium
Hypothesis: Does inhibition of basolateral membrane proteins inhibit chloride secretion through apical CFTR?
0 10 20 30 40 50 60 70 80 90 1000
500
1000
1500
2000
2500
R3
Time (min)
Ch
lori
de
Se
cre
tio
n (
µE
q/h
/g)
BasalF + I Bumet
F + IF + I Ouabain
F + IF + I
0 10 20 30 40 50 60 70 80 90 1000
500
1000
1500
2000
2500
R4
Time (min)
Ch
lori
de
Se
cre
tio
n (
µE
q/h
/g)
F + I F + IBasal F + IBaCl2F + I
Ouabain + BaCl2F + I
Conclusions
• Bumetanide inhibits cotransporter• Ouabain inhibits the ATPase enzyme, which in
turn inhibits the cotransporter• Barium chloride inhibits by depolarization
Future Suggested Experiments
• Administer bumetanide and barium chloride• All three drugs• Change the order the drugs are administered • Vary the perfusion times for each drug• Change the basal solution composition• Increase extracellular potassium
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