1. How do epithelia pump water?
2. What is the mechanism of intestinal Cl- induced fluid secretion?
3. What is the main point of regulation of the above?
4. Describe mech of regulation when this is on (cAMP)
5. When it's off (cAMP)
6. When it's back on again (cAMP)
1. Pumps salt and water follows osmotically (salt goes from BL blood side to apical side)
1. BL side: Na-K-Cl cotransporter (brings in Na, 2 Cl, K+) AND Na-K ATPase (3Na+ out, 2 K+ in) and K+ ion transporter (1 K+ out)
2. Cl- flows across cell from BL side to apical side, creating negative potential charge on apical side.
3. Na+ ions follow Cl-, moving through leaky tight junctions from BL to apical side (paracellular)
4. H2O follows Na+ transcellularly through water channels in protein.
Summary: transcellular movement of Cl-, paracellular movement of Na+, transcellular movement of H2O.
3. Apical chloride channel
4. Activated by phosphorylation by protein kinase (cAMP-dep kinase A or membrane-bound cGMP-dep kinase).-(1) Phosphorylation of channel --> (2) activation & opens channel --> (3) allows Cl-ions to pass through --> (4) Na+ passes through --> (5) water follows.
5. Dephosphorylation --> Cl- can't leave --> [Cl-] builds up --> no more entry of Cl-
6. Then, (1) hormone comes along, stimulating secretion --> (2) binds to basolateral receptor --> (3) activating G protein --> (4) activates adenylate cyclase (BL membrane): ATP --> cAMP. (5) Binds to PKA, (6) phosphorylates Cl-channel, then as (7) chloride drops, (8) Cl-enters, and (9) water can move again.
7. Guanylate cyclases-C (apical membrane) activated can activate cGMP which activates PKG (which can also regulate pathway similarly).
Basically, phosphorylated = active.