Enhancement of P2Y6-induced Cl- secretion by IL-13 and modulation of SK4 channels activity in human bronchial cells.
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.
Dulong
Sandrine
S
Laboratoire de Physiologie Cellulaire et Moléculaire, Université de Nice-Sophia Antipolis, Nice, France.
Bernard
Karen
K
Ehrenfeld
Jordi
J
D000838:Anions / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry / Q000378:metabolism*; D003022:Clotrimazole / Q000494:pharmacology; D004594:Electrophysiology; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013997:Time Factors; D014530:Uridine Diphosphate / Q000494:pharmacology
D000838:Anions; D002712:Chlorides; D018793:Interleukin-13; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D015759:Ionomycin; D014530:Uridine Diphosphate; D003022:Clotrimazole