Distal colonic K+ secretion occurs via BK channels

K+ secretion in the kidney and distal colon is a main determinant of K+ homeostasis. This study investigated the identity of the relevant luminal secretory K+ ion channel in distal colon. An Ussing chamber was used to measure ion transport in the recently generated BK channel-deficient (BK-/-) mice. BK-/- mice display a significant colonic epithelial phenotype with (1) lack of Ba2+-sensitive resting K+ secretion, (2) absence of K+ secretion stimulated by luminal P2Y(2) and P2Y(4) receptors, (3) absence of luminal Ca2+ ionophore (A23187)-stimulated K+ secretion, (4) reduced K+ and increased Na+ contents in feces, and (5) an increased colonic Na+ absorption. In contrast, resting and uridine triphosphate (UTP)-stimulated K+ secretion was not altered in mice that were deficient for the intermediate conductance Ca2+-activated K+ channel SK4. BK channels localize to the luminal membrane of crypt, and reverse transcription-PCR results confirm the expression of the BK channel a-subunit in isolated distal colonic crypts. It is concluded that BK channels are the responsible K+ channels for resting and stimulated Ca2+-activated K+ secretion in mouse distal colon.