CFTR‐mediated Secretion is Supported by Different Basolateral Transporters in Juvenile Murine Proximal Colon

Abstract

Multiple basolateral uptake mechanisms for Cl and HCO3 are stimulated to sustain transepithelial anion secretion during activation of CFTR by cyclic nucleotides. We hypothesized AE2 has a greater contribution in juvenile murine colon and that activity of NBCs are increased in adult colon. Short‐circuit current (Isc) responses were measured in muscle‐stripped proximal colon isolated from juvenile and adult wild‐type mice. In Cl and HCO3 containing Ringers, juvenile and adult proximal colon exhibited no differences in cAMP‐stimulated currents. However, juvenile proximal colon exhibited decreased sensitivity to the distilbene SITS, suggesting reduced activity of either NBC or AE2 in juvenile proximal colon. Blocking of coupled AE2/NHE1 (EIPA) reduced the Isc response to cAMP and SITS in juvenile but not adult proximal colon. Cl‐free Ringers significantly reduced the Isc response to cAMP in both adult and juvenile proximal colon. Under this condition, the SITS‐sensitive Isc was still reduced in juvenile, as compared to adult, proximal colon, further supporting the hypothesis that SITS‐sensitive NBC activity is lower in juvenile colon. Current studies are focused on whether these changes result from alterations in transporter expression or activity. We conclude that coupled NHE1/AE2 activity is increased and SITS‐sensitive NBC activity is decreased in juvenile proximal colon. Supported by AGA‐FDHN.