Abstract:

In secretory epithelia, basolateral membrane K+ channels regulate membrane potential, a driving force for anion secretion. The molecular identity of these channels and mechanisms regulating them are unclear. The central hypothesis of this work is that these channels are KCNQ1 which is activated by the secretory neurotransmitter, vasoactive intestinal peptide (VIP). Cultured T84 human colonic cells, Mz-ChA-1 human bile duct cells, and NRC rat bile duct cells were used. When monolayers of T84 cells were short-circuited, serosal addition of VIP stimulated a current (I sc ) which barium ion (Ba2+ ) inhibited. Transfection of these monolayers with short interfering RNA (siRNA) designed to degrade KCNQ1 mRNA significantly reduced the VIP-stimulated Isc . VIP activated a Ba2+ -sensitive K+ current in perforated patch voltage-clamped T84 cells and Mz-ChA-1 cells. VIP failed to stimulate I sc or K+ current in NRC cells. These data suggest that anion secretion by liver ducts and intestinal crypts is dependent on KCNQ1.