Our previous study demonstrated upregulation of voltage-gated K+ channels (Kv) in colonic carcinoma. These Kv channels were shown to support cell proliferation. Here we examined the electrophysiological properties of the proximal and distal colon in the intestine cancer mouse model C57BL/6J-Min/+ (Apcmin/+ ). After a weight loss of 10%, Apcmin/+ mice were sacrificed and proximal and distal colon were removed. Wild type (wt+/+ ) mice of the same age served as controls. Apcmin/+ mice developed numerous adenomatous polyps in both small and large intestine. Apcmin/+ mice showed largely enhanced amiloride sensitive Na+ transport in distal colon. Moreover, Na+ transport could be detected in the proximal colon of Apcmin/+ but not in wt+/+ mice. These results were confirmed by real time PCR, immunohistochemisty and western blot analysis. Beside Na+ transport, b subunits of BKca channels were upregulated in Apcmin/+ colon as demonstrated by real time PCR technique. There results indicated that the reduced expression of a tumor suppressor gene is parallel by changes in ion channel expression and function.

Supported by DFG SCHR 752/2-1, SCHR 752/2-2 and Wilhelm

Sander Stiftung 2005.063.1