Intact colonic KCa1.1 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 Ca2+‐activated K+ channel (KCa1.1) is well established as the sole, but highl...

Full description

Saved in:
Bibliographic Details
Published in:Physiological reports 2017-03, Vol.5 (5), p.n/a
Main Authors: Larsen, Casper K., Praetorius, Helle A., Leipziger, Jens, Sorensen, Mads V.
Format: Article
Language:English
Subjects:
BK channel
K+ Homeostasis
K+ secretion
KCa1.1
KCa1.1 beta2 subunit
LRCC26
Maxi K+ channel
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 β and γ subunits of the pore‐forming α‐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 only β‐subunit of the colonic enterocyte KCa1.1 channel. We can report that: (1) Neither KCa1.1 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 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 γ‐subunits of the KCa1.1 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 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 β2‐subunit of KCa1.1 channel complex despite no additional compensatory induction of KCa1.1 β‐subunits. Intact barium sensitive short circuit current in freshly isolated colonic epithelia from KCNMB2 knockout mice.
ISSN:2051-817X
DOI:10.14814/phy2.13179