title: Intact colonic KCa1.1 channel activity in KCNMB2 knockout mice.
abstract: 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 auxiliaryβandγsubunits of the pore-formingα-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-β2-subunit (KCNMB2-/-), which apparently is the onlyβ-subunit of the colonic enterocyte KCa1.1 channel. We can report that: (1) Neither KCa1.1α- nor the remainingβ-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 auxiliaryγ-subunits of the KCa1.1 channel has been described. (5) We detected theγ1-subunit (LRRC26) mRNA in colonic epithelia. To investigate the physiological role of theγ1-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 theβ2-subunit of KCa1.1 channel complex despite no additional compensatory induction of KCa1.1β-subunits.
authors.affiliation: Department of Biomedicine, Physiology Health, Aarhus University, Aarhus C, Denmark.
authors.forename: Casper K
authors.initials: CK
authors.lastname: Larsen
authors.affiliation: Department of Biomedicine, Physiology Health, Aarhus University, Aarhus C, Denmark.
authors.forename: Helle A
authors.initials: HA
authors.lastname: Praetorius
authors.affiliation: Department of Biomedicine, Physiology Health, Aarhus University, Aarhus C, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Leipziger
authors.affiliation: Department of Biomedicine, Physiology Health, Aarhus University, Aarhus C, Denmark mvs@biomed.au.dk.|Aarhus Institute for Advanced Studies (AIAS), Aarhus University. Hoegh-Guldbergs, Aarhus C, Denmark.
authors.forename: Mads V
authors.initials: MV
authors.lastname: Sorensen
mesh_terms: D000450:Aldosterone; D000818:Animals; D001692:Biological Transport; D003106:Colon / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism*
chemical_list: C465449:Kcnma1 protein, mouse; C000609143:Kcnmb2 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D000450:Aldosterone; D011188:Potassium
keywords: BK channel; K+ Homeostasis; K+ secretion; KCa1.1; KCa1.1 beta2 subunit; LRCC26; Maxi K+ channel