Physiology 3120 Lecture Notes - Cholera Toxin, Symporter, Diarrhea
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Wednesday, April 7, 2010
Sodium transport (cont’d)
•Primarily in the lower gut. Typified by secondary active transport using a Na/Cl symporter (1:1 ratio);
the transporter is activated by a Na concentration gradient across the apical/luminal membrane. Binding
of the Na (already has high affinity) increases the affinity for the Cl site for its substrate (i.e. chloride);
when both ions bind, the protein undergoes some conformational change occurs to move the ions to the
cytosolic side. On basolateral membrane, have a Na ATPase: functions to pump Na into blood, as well
as maintain Na concentration across apical membrane (maintains high affinity for Na binding site); also
have chloride channels here, so chloride drifts into EC compartment
•Pathological situation where the above process is eliminated or overcome; associated with watery
diarrhoea and cholera. Increase in content of prostaglandin E2 associated with cholera toxin. Cholera
toxin does 2 things: (1) inhibits apical Na/Cl symporter, so can’t absorb NaCl, and (2) punches holes in
apical membrane, causing Cl to leak out into the intestinal lumen (and water to follow). PGE2 is specific
to the Na/Cl symporter, so giving electrolyte-rich juice (Ginger-Ale) can help overcome the net efflux of
Solvent drag: solvent moves and drags all other substances dissolved in it along for the ride
•First digested by amylase in the mouth; followed by pancreatic enzymes (amylase, which is the same)
in the duodenum. These two amylases are so efficient, that you end up with a solution of
monosaccharides and disaccharides (you ONLY absorb carbs in the form of monosaccharides, so
need to digest the disaccharides). In the brush border epithelium of the intestine, there are enzymes that
digest certain disaccharides (i.e. lactase, sucrase, maltase, etc.) that are synthesized in the active form.
•Glucose is absorbed by a similar mechanism as Na & Cl. Galactose is absorbed similarly, so the
cotransporter is not as specific as the Na/Cl transporter.
Has an apically-located transporter that has a Na site and a glucose site (2:1), but still requires
Na concentration gradient across apical membrane, which is maintained by basolaterally
located Na ATPase. Glucose has several routes out of the cell: (1) glucose channels that are
large enough to carry it, (2) protein that carries glucose across basolateral membrane that
does NOT require ATP (no Na requirement). If too much glucose is absorbed, a net positivity
accumulates in the cell, creating an unfavourable concentration gradient for other cations.
Travels across without Na necessity. Has an apical and a basolateral carrier. Gatorade (which
once contained a lot of glucose and caused high levels of K secretion) now uses fructose as its
sugar because it doesn’t require a cation for cotransport, and therefore doesn’t cause a build-up
of positive charge inside the cell.
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