Interleukin-1β suppresses activity of an inwardly rectifying K+ channel in human renal proximal tubule cells

We investigated the effect of interleukin-1 beta (IL-1 beta) on activity of an inwardly rectifying K+ channel in cultured human proximal tubule cells (RPTECs), using the patch-clamp technique and Fura-2 Ca2+ imaging. IL-1 beta (15 pg/ml) acutely reduced K+ channel activity in cell-attached patches. This effect was blocked by the IL-1 receptor antagonist (20 ng/ml), an inhibitor of phospholipase C, neomycin (300 mu M), and an inhibitor of protein kinase C (PKC), GF109203X (500 nM). The Fura-2 Ca2+ imaging revealed that IL-1 beta increased intracellular Ca2+ concentration even after removal of extracellular Ca2+, which was blocked by an inhibitor of inositol 1,4,5-trisphosphate receptors, 2-aminoethoxydiphenyl borate (2-APB, 1 mu M). Moreover, IL-1 beta suppressed channel activity in the presence of 2-APB without extracellular Ca2+. These results suggest that IL-1 beta suppresses K+ channel activity in RPTECs through binding to its specific receptor and activation of the PKC pathway even though intracellular Ca2+ does not increase.