NPPB block of the intermediate conductance Ca2+-activated K+ channel

We have shown that the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) also blocks the intermediate-conductance Ca2+-activated K (IKCa) current in human leukemic HL-60 and glioblastoma GL-15 cell lines. The macroscopic IKCa current was activated by ionomycin plus 1-EBIO, and identified as intermediate conductance by being fully blocked by charybdotoxin, clotrimazole, nitrendipine (L-type Ca2+ channel blocker), and NS1619 (BKCa channel opener), but not by D-tubocurarine or TEA. The IKCa current was blocked by NPPB in a reversible dose-dependent manner, with an IC50 of 39 muM in HL-60 and 125 M in GL-15 cells. The block of the IKCa current was also recorded at the single channel level in excised inside-out patches. As expected, NPPB also blocked the volume-activated Cl- current expressed by GL-15 cells, with an IC50 of 44 muM. The functional implications of IKCa current block by NPPB are discussed. (C) 2004 Elsevier B.V. All rights reserved.