Busch A E, Suessbrich H, Waldegger S, Sailer E, Greger R, Lang H, Lang F, Gibson K J, Maylie J G
Institute of Physiology, Eberhard-Karls-Universität Tübingen, Gmelinstrasse 5, D-72076 Tübingen, Germany.
Pflugers Arch. 1996 Oct;432(6):1094-6. doi: 10.1007/s004240050240.
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 IsK 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 IKs and IKr, and for the cloned guinea pig IsK channel and the human HERG channel, which underly IKs and IKr, respectively, was analyzed. 293B inhibited both the slowly activating K+ conductance IKs in cardiac myocytes and guinea pig IsK channels expressed in Xenopus oocytes with a similar IC50 (2-6 micromol/l). In contrast, high concentrations of 293B had only a negligible effect on the more rapid activating IKr. Similarly, 293B exerted no effect on HERG channels expressed in Xenopus oocytes. In summary, 293B appears to be a rather specific inhibitor of IKs and the underlying IsK channels.
色满醇衍生物293B先前已被证明可抑制大鼠结肠隐窝中一种受cAMP调节的钾离子电导。随后对来自大鼠的克隆钾离子通道的研究表明，293B可特异性阻断非洲爪蟾卵母细胞中表达的IsK通道，但分别不影响延迟整流钾通道Kv1.1和内向整流钾通道Kir2.1。在本研究中，分析了293B对心脏钾离子电导IKs和IKr，以及对分别构成IKs和IKr的克隆豚鼠IsK通道和人HERG通道的特异性。293B以相似的IC50（2 - 6微摩尔/升）抑制心肌细胞中缓慢激活的钾离子电导IKs和非洲爪蟾卵母细胞中表达的豚鼠IsK通道。相反，高浓度的293B对更快激活的IKr只有可忽略不计的影响。同样，293B对非洲爪蟾卵母细胞中表达的HERG通道没有作用。总之，293B似乎是IKs及其基础IsK通道的一种相当特异性的抑制剂。
