Expression of functional P2Y 6 receptors was demonstrated in primary cultures of human bronchial cells (NHBE cells). P2Y 6 receptors were located only on the apical membranes of NHBE cells. Their stimulation by UDP induced a chloride secretion (short-circuit current) reflected by the development of two I sc components (I fast and I late ). A pharmacological characterization of those two I sc components showed the involvement of CaCC and CFTR channel activity in I fast and I late respectively. I fast was also found to be under control of basolateral SK4 channels. Indeed, inhibition of SK4 channels opening by clotrimazole dramatically reduced I fast amplitude. The epithelial ion transporting phenotype depends on the cellular state of differentiation. As previously reported, we observed that Ultroser G increased the epithelial tightness and Na + -transport capacity while IL-13 switch the epithelial ion transport phenotype from a Na + -absorbing to a Cl - -secreting one. In our study, we report for the first time a change in the K + cell permeability associated to IL-13-induced cell differentiation. IL-13 treatment increased the-resting K + permeability as well as the Ca 2+ -dependent K + permeability stimulated by UDP or ionomycin. SK4 channels activity, underlying the Ca 2+ -dependent K + permeability was in particular increased by IL-13. The on/off effect of IL-13 on P2Y 6 -induced Cl-secretion may help to identify the molecular determinants responsible for the CaCC channel activity. Copyright © 2007 S. Karger AG.