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Intact colonic K+ secretion in KCNMB2 knockout mice
Author(s) -
Larsen Casper Kornbech,
Praetorius Helle Anette,
Leipziger Jens
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1162.2
Subject(s) - secretion , protein subunit , ussing chamber , patch clamp , chemistry , knockout mouse , downregulation and upregulation , potassium channel , medicine , endocrinology , microbiology and biotechnology , receptor , biology , biochemistry , gene
Colonic K + secretion occurs via the pump‐leak mechanism; K + is taken up from the basolateral side via the Na + /K + pump and NKCC1 and leaves the cells via apical K + channels. The BK channel has been identified as the relevant K + channel involved in K+ secretion in mammalian distal colon. It consists of 4 α‐subunits (encoded by KCNMA1) and 4 modulatory β‐subunits, of which there are 4 isoforms (KCNMB1–4). Previously, we have shown that the β 2 ‐(KCNMB2) is the only β‐subunit expressed in the murine distal colon and that aldosterone increases the expression of both the α‐ and the β2‐subunit. We hypothesize that upregulation of the β2‐subunit participates in aldosterone‐induced colonic K + secretion. Here we use a global β2 subunit (KCNMB2) knockout mouse, in which we study distal colonic K + secretion by open‐circuit recordings in Ussing chamber. The luminal Ba 2+ ‐sensitive short circuit current was taken as measure of BK channel‐mediated electrogenic K + secretion. Resting K + secretion was 20.8 μA·cm −2 ± 3.8 and 28.2 μA·cm −2 ± 4.4 in WT and KO tissue, respectively (n=6). We found that apical ATP, known to activate K + secretion via luminal P2Y receptors, increased colonic K + secretion to −127.2 μA·cm −2 ± 9.47 (WT) and −73.4 μA·cm −2 ± 4.9 (KO) We report the surprising finding that knockout of the assumed β‐subunit (KCNMB2) of the BK channel leaves resting and ATP‐stimulated K + secretion intact. Supported by the Lundbeck foundation.