Collectively, these results indicated that 1-EBIO augments CFTR-mediated Cl− secretion in human colon in the presence of cAMP stimulation by activation of the basolateral Ca2+-activated KCNN4 K+ channel, but not the cAMP-dependent KCNQ1/KCNE3 K+ channel complex, and suggested that 1-EBIO may potentiate residual CFTR-mediated Cl− secretion in CF tissues via this mechanism. Here, KCNE3 is linked to cystic fibrosis.