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 Ba 2+ -sensitive resting K + secretion, ( 2 ) absence of K + secretion stimulated by luminal P2Y 2 and P2Y 4 receptors, ( 3 ) absence of luminal Ca 2+ 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 Ca 2+ -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 α-subunit in isolated distal colonic crypts. It is concluded that BK channels are the responsible K + channels for resting and stimulated Ca 2+ -activated K + secretion in mouse distal colon.