中电导钙激活钾通道的NPPB阻断作用

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

作者信息

Fioretti Bernard, Castigli Emilia, Calzuola Isabella, Harper Alexander A, Franciolini Fabio, Catacuzzeno Luigi

机构信息

Dipartimento Biologia Cellulare e Molecolare, Universita' di Perugia Via Pascoli 1, I-06123 Perugia, Italy.

出版信息

Eur J Pharmacol. 2004 Aug 16;497(1):1-6. doi: 10.1016/j.ejphar.2004.06.034.

DOI:10.1016/j.ejphar.2004.06.034

PMID:15321728

Abstract

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.

摘要

我们已经表明，氯离子通道阻滞剂5-硝基-2-（3-苯丙基氨基）苯甲酸（NPPB）也可阻断人白血病HL-60细胞系和胶质母细胞瘤GL-15细胞系中的中电导钙激活钾（IK(Ca)）电流。宏观IK(Ca)电流由离子霉素加1-EBIO激活，并通过被蝎毒素、克霉唑、尼群地平（L型钙通道阻滞剂）和NS1619（大电导钙激活钾通道开放剂）完全阻断而被鉴定为中电导，但不被筒箭毒碱或四乙铵阻断。IK(Ca)电流被NPPB以可逆的剂量依赖性方式阻断，在HL-60细胞中的IC(50)为39微摩尔，在GL-15细胞中为125微摩尔。在切除的内向外膜片中，IK(Ca)电流的阻断也在单通道水平上被记录到。正如预期的那样，NPPB也阻断了GL-15细胞表达的容积激活氯离子电流，IC(50)为44微摩尔。本文讨论了NPPB阻断IK(Ca)电流的功能意义。