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 Ca(2+)-activated K(+) (IK(Ca)) current in human leukemic HL-60 and glioblastoma GL-15 cell lines. The macroscopic IK(Ca) current was activated by ionomycin plus 1-EBIO, and identified as intermediate conductance by being fully blocked by charybdotoxin, clotrimazole, nitrendipine (L-type Ca(2+) channel blocker), and NS1619 (BK(Ca) channel opener), but not by D-tubocurarine or TEA. The IK(Ca) current was blocked by NPPB in a reversible dose-dependent manner, with an IC(50) of 39 microM in HL-60 and 125 microM in GL-15 cells. The block of the IK(Ca) 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 IC(50) of 44 microM. The functional implications of IK(Ca) current block by NPPB are discussed.
Dipartimento Biologia Cellulare e Molecolare, Universita' di Perugia Via Pascoli 1, I-06123 Perugia, Italy. fabiolab@unipg.it
Bernard
B
Fioretti
Emilia
E
Castigli
Isabella
I
Calzuola
Alexander A
AA
Harper
Fabio
F
Franciolini
Luigi
L
Catacuzzeno
D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009579:Nitrobenzoates / Q000008:administration & dosage / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000502:physiology
D018118:Chloride Channels; D009579:Nitrobenzoates; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid