| First Author | Larsen CK | Year | 2017 |
| Journal | Physiol Rep | Volume | 5 |
| Issue | 5 | PubMed ID | 28292889 |
| Mgi Jnum | J:240672 | Mgi Id | MGI:5888924 |
| Doi | 10.14814/phy2.13179 | Citation | Larsen CK, et al. (2017) Intact colonic KCa1.1 channel activity in KCNMB2 knockout mice. Physiol Rep 5(5) |
| abstractText | 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 Ca2+-activated K+ channel (KCa1.1) is well established as the sole, but highly regulated apical K+ conductance. The physiological importance of auxiliary beta and gamma subunits of the pore-forming alpha-subunit of the KCa1.1 channel is not yet fully established. This study investigates colonic K+ secretion in a global knockout mouse of the KCa1.1-beta2-subunit (KCNMB2-/-), which apparently is the only beta-subunit of the colonic enterocyte KCa1.1 channel. We can report that: (1) Neither KCa1.1 alpha- nor the remaining beta-subunits were compensatory transcriptional regulated in colonic epithelia of KCNMB2-/- mice. (2) Colonic epithelia from KCNMB2-/- mice displayed equal basal and ATP-induced KCa1.1-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 KCa1.1 channel iberiotoxin in both KCNMB2+/+ and KCNMB2-/- mice. Recently a novel family of auxiliary gamma-subunits of the KCa1.1 channel has been described. (5) We detected the gamma1-subunit (LRRC26) mRNA in colonic epithelia. To investigate the physiological role of the gamma1-subunit of KCa1.1 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 beta2-subunit of KCa1.1 channel complex despite no additional compensatory induction of KCa1.1 beta-subunits. |
