Intact colonic K C a 1.1 channel activity in KCNMB 2 knockout mice

Mammalian potassium homeostasis results from tightly regulated renal and colonic excretion, which balances the unregulated dietary K + intake. Colonic K + secretion follows the pump‐leak model, in which the large conductance Ca 2+ ‐activated K + channel ( K C a 1.1 ) is well established as the sole, but highly regulated apical K + conductance. The physiological importance of auxiliary β and γ subunits of the pore‐forming α ‐subunit of the K C a 1.1 channel is not yet fully established. This study investigates colonic K + secretion in a global knockout mouse of the K C a 1.1‐ β 2‐subunit ( KCNMB 2 −/− ), which apparently is the only β ‐subunit of the colonic enterocyte K C a 1.1 channel. We can report that: (1) Neither K C a 1.1 α ‐ nor the remaining β ‐subunits were compensatory transcriptional regulated in colonic epithelia of KCNMB 2 −/− mice. (2) Colonic epithelia from KCNMB 2 −/− mice displayed equal basal and ATP ‐induced K C a 1.1‐mediated K + conductance as compared to KCNMB 2 +/+ . (3) K + secretion was increased in KCNMB 2 −/− epithelia compared to wild‐type epithelia from animals fed an aldosterone‐inducing diet. (4) Importantly, the apical K + conductance was abolished by the specific blocker of K C a 1.1 channel iberiotoxin in both KCNMB 2 +/+ and KCNMB 2 −/− mice. Recently a novel family of auxiliary γ ‐subunits of the K C a 1.1 channel has been described. (5) We detected the γ 1‐subunit ( LRRC 26) mRNA in colonic epithelia. To investigate the physiological role of the γ 1‐subunit of K C a 1.1 channels in colonic K + secretion, we acquired an LRRC 26 knockout mouse. (6) Unexpectedly, LRRC 26 mice had a perinatal lethal phenotype, thus preventing functional measurements. On this basis we conclude that colonic K + secretion is intact or even increased in mice lacking the β 2‐subunit of K C a 1.1 channel complex despite no additional compensatory induction of K C a 1.1 β ‐subunits.