Tu1390 Anoctamin 6 Contributes to Accessory Cholera Enterotoxin (ACE) Stimulated Chloride Secretion in Intestinal Epithelial Cells to Induced Diarrhea

Abstract

) than in control patients (0.28 ± 0.04 mS.cm-2 , P<0.001), but this increase in GSK did not compensate for the decrease in basolateral membrane conductance (from 22 mS.cm-2 to 5 mS.cm -2 ) previously attributed to decreased IK channel expression/activity in UC (J Pathol 2012;226:463-470). In control crypts, 10μM forskolin and 1μM thromboxane A2 stimulated channel activity 30-fold (n=8, P<0.005) and 10-fold (n=5, P<0.05) respectively, while 100nM PGE 2, 10nM IL-1β and 1μM LTD4 had no effect. Conclusions: Crypt cells in normal human colon express cAMP-activated KCNQ1/ KCNE3 channels which make a far smaller contribution to overall basolateral conductance than IK channels. In active UC, KCNQ1/KCNE3 channel activity is significantly increased, but this fails to compensate for the depolarizing effect of decreased IK channel expression/ activity. This may explain, at least in part, why defective electrogenic Na+ absorption rather than increased electrogenic Cl˜- secretion is the dominant pathophysiological mechanism of diarrhea in active UC (J Pathol 2012;226:463-470).