Intact colonic K1.1 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-activated K channel (K1.1 is well established as the sole, but highly regulated apical K conductance. The physiological importance of auxiliary and subunits of the pore-forming -subunit of the K1.1 channel is not yet fully established. This study investigates colonic K secretion in a global knockout mouse of the K1.1-2-subunit (KCNMB2), which apparently is the only -subunit of the colonic enterocyte K1.1 channel. We can report that: (1) Neither K1.1 - nor the remaining -subunits were compensatory transcriptional regulated in colonic epithelia of KCNMB2 mice. (2) Colonic epithelia from KCNMB2 mice displayed equal basal and ATP-induced K1.1-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 K1.1 channel iberiotoxin in both KCNMB2 and KCNMB2 mice. Recently a novel family of auxiliary -subunits of the K1.1 channel has been described. (5) We detected the 1-subunit (LRRC26) mRNA in colonic epithelia. To investigate the physiological role of the 1-subunit of K1.1 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 2-subunit of K1.1 channel complex despite no additional compensatory induction of K1.1 -subunits.