The KCNQ1 potassium channel (alpha -subunit can associate with various KCNE
beta -subunits that drastically influence channel gating. Here we show tha
t in the mouse gastrointestinal tract KCNQ1 is prominently expressed in sto
mach, small intestine and colon, while KCNE3 is expressed in the colon and
to a lesser extent in small intestine. Immunostaining revealed that KCNQ1 c
olocalizes with KCNE3 in the basolateral membranes of crypt cells of the co
lon and small intestine. Together with the previously shown electrophysiolo
gical properties of KCNQ1/KCNE3 channels, this strongly suggests that they
form the basolateral potassium conductance that is required for transepithe
lial cAMP-stimulated chloride secretion. In the stomach. KCNQ1 is expressed
together with the H+/K+-ATPase in the luminal membrane of acid-secreting p
arietal cells of gastric glands. KCNE2. but neither KCNE1 nor KCNE3 was det
ected in the stomach by Northern analysis. Similar to KCNQ1, KCNE2 was pres
ent in gastric glands in only a subset of cells that probably represent par
ietal cells. The coexpression of KCNQ1 and KCNE2 in HEK293 cells yielded po
tassium currents that were open at resting voltages, suggesting that these
heteromeric channels may underlie the apical potassium conductance in acid-
secreting parietal cells that is necessary for the recycling of potassium i
ons during acid secretion via the H+/K+-ATPase.