Inhibition of I-Ks in guinea pig cardiac myocytes and guinea pig I-sK channels by the chromanol 293B
Inhibition of I-Ks in guinea pig cardiac myocytes and guinea pig I-sK channels by the chromanol 293B
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DOI：
10.1007/s004240050240
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发表时间：
1996-10-01
影响因子：
4.5
通讯作者：
Maylie, JG
中科院分区：
文献类型：
--
作者：
Busch, AE;Suessbrich, H;Maylie, JG
此前已证明色原醇衍生物293 B可抑制大鼠结肠隐窝中cAMP调节的K+电导。随后对大鼠克隆的K+通道的研究表明，293 B特异性阻断爪蟾卵母细胞中表达的I-sK通道，但不影响延迟整流和内向整流Kv1.1和KiR2.1。在本研究中，分析了293 B对心脏K+电导I-Ks和I-Kr的特异性，以及对克隆的豚鼠I-sK通道和人HERG通道的特异性，所述通道分别是I-Ks和I-Kr的基础。293 B抑制心肌细胞中缓慢激活的K+电导I-Ks和爪蟾卵母细胞中表达的豚鼠I-sK通道，IC 50相似（2-6 μ mol/l）。相比之下，高浓度的293 B对更快速活化I-Kr的影响可以忽略不计。类似地，293 B对爪蟾卵母细胞中表达的HERG通道没有影响。总之，293 B似乎是I-Ks和潜在的I-sK通道的相当特异性的抑制剂。
The chromanol derivative 293B was previously shown to inhibit a cAMP regulated K+ conductance in rat colon crypts. Subsequent studies on cloned K+ channels from the rat demonstrated that 293B blocks specifically I-sK channels expressed in Xenopus oocytes, but does not affect the delayed and inward rectifier Kv1.1 and KiR2.1, respectively. In the present study, the specificity of 293B for the cardiac K+ conductances I-Ks and I-Kr, and for the cloned guinea pig I-sK channel and the human HERG channel, which underly I-Ks and I-Kr, respectively, was analyzed. 293B inhibited both the slowly activating K+ conductance I-Ks in cardiac myocytes and guinea pig I-sK channels expressed in Xenopus oocytes with a similar IC50 (2-6 mu mol/l). In contrast, high concentrations of 293B had only a negligible effect on the more rapid activating I-Kr. Similarly, 293B exerted no effect on HERG channels expressed in Xenopus oocytes. In summary, 293B appears to be a rather specific inhibitor of I-Ks and the underlying I-sK channels.