Opening of large-conductance calcium-activated potassium channels by the substituted benzimidazolone NS004.
Opening of large-conductance calcium-activated potassium channels by the substituted benzimidazolone NS004.
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通过取代的苯并咪唑酮 NS004 打开大电导钙激活钾通道。
DOI：
10.1152/jn.1994.71.5.1873
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发表时间：
1994
影响因子：
2.5
通讯作者：
Gribkoff,VK
中科院分区：
文献类型：
--
作者：
McKay,MC;Dworetzky,SI;Meanwell,NA;Olesen,SP;Reinhart,PH;Levitan,IB;Adelman,JP;Gribkoff,VK
1.我们采用电生理技术研究了5-三氟甲基-1-（5-氯-2-羟基苯基）-1，3-二氢-2H-苯并咪唑-2-酮（NS 004）对大电导钙激活钾（BK）通道的作用。2.我们使用记录从切除的膜补丁（细胞贴附和由内而外的单通道配置）和全细胞膜片钳记录检查的影响，NS 004对单个BK通道和全细胞外向电流，分别在大鼠GH 3克隆垂体瘤细胞。我们还测试了NS 004上的电压钳位BK通道从大鼠脑质膜制剂分离和重组成平面脂质双层。最后，我们使用双电极电压钳技术研究NS 004对最近描述的果蝇Slo BK克隆在非洲爪蟾卵母细胞中表达的电流的影响。3.在GH 3细胞和表达Slo基因产物NS 004的非洲爪蟾卵母细胞中，分别产生了伊比利亚毒素或四乙铵敏感性全细胞外向电流的增加。NS 004产生了一个显着增加的活性，单个GH 3细胞BK通道和大鼠脑BK通道重建成平面脂质双层。在这两个系统中，其特征在于通道平均开放时间的增加，脉冲串间隔的减少，以及通道电压/钙敏感性的明显增加。4.这些数据表明，NS 004可能是有用的研究BK通道的生物物理和分子特性，并确定BK通道开放的功能后果。
1. We used electrophysiological techniques to examine the effects of 5-trifluoromethyl-1-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-2H-benzimidaz ole- 2-one (NS004) on large-conductance calcium-activated potassium (BK) channels. 2. We used recordings from excised membrane patches (cell-attached and inside-out single-channel configurations) and whole-cell patch-clamp recordings to examine the effects of NS004 on single BK channels and whole-cell outward currents, respectively, in rat GH3 clonal pituitary tumor cells. We also tested NS004 on voltage-clamped BK channels isolated from rat brain plasma membrane preparations and reconstituted into planar lipid bilayers. Finally, we used two-electrode voltage-clamp techniques to study the effects of NS004 on currents expressed in Xenopus laevis oocytes by the recently described Slo BK clone from Drosophila. 3. In GH3 cells and in Xenopus oocytes expressing the Slo gene product NS004 produced an increase in an iberiotoxin- or tetraethylammonium-sensitive whole-cell outward current, respectively. NS004 produced a significant increase in the activity of single GH3 cell BK channels and rat brain BK channels reconstituted into planar lipid bilayers. In both systems this was characterized by an increase in channel mean open time, a decrease in interburst interval, and an apparent increase in channel voltage/calcium sensitivity. 4. These data indicate that NS004 could be useful for investigating the biophysical and molecular properties of BK channels and for determining the functional consequences of the opening of BK channels.