Intact colonic K(C) (a)1.1 channel activity in KCNMB2 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‐β2‐subunit (KCNMB2(−/−)), 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 KCNMB2(−/−) mice. (2) Colonic epithelia from KCNMB2(−/−) mice displayed equal basal and ATP‐induced K(C) (a)1.1‐mediated K(+) conductance as compared to KCNMB2(+/+). (3) K(+) secretion was increased in KCNMB2(−/−) 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 KCNMB2(+/+) and KCNMB2(−/−) mice. Recently a novel family of auxiliary γ‐subunits of the K(C) (a)1.1 channel has been described. (5) We detected the γ1‐subunit (LRRC26) mRNA in colonic epithelia. To investigate the physiological role of the γ1‐subunit of K(C) (a)1.1 channels in colonic K(+) secretion, we acquired an LRRC26 knockout mouse. (6) Unexpectedly, LRRC26 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 β2‐subunit of K(C) (a)1.1 channel complex despite no additional compensatory induction of K(C) (a)1.1 β‐subunits.