Heath B M, Terrar D A
University Department of Pharmacology, Oxford, United Kingdom.
Cardiovasc Res. 1994 Jun;28(6):818-22. doi: 10.1093/cvr/28.6.818.
The aim was to investigate the effect of activation of ATP sensitive potassium channels by cromakalim on the delayed rectifier potassium current (IK) in guinea pig ventricular myocytes. Experiments were carried out in the absence and presence of forskolin or isoprenaline to promote phosphorylation of IK, and in the presence of glibenclamide to block the ATP sensitive potassium current (IK(ATP)).
Single cells were isolated from guinea pig ventricle. Potassium currents were studied under voltage clamp conditions. The delayed rectifier was measured as an outward tail current upon repolarisation to a holding potential of -40 mV following depolarising steps to +40 mV. Induction of IK(ATP) was indicated by changes in the holding current.
Exposure to 20 microM cromakalim caused a significant increase of 244(SEM 47)% in the holding current and simultaneous decreases of 22(5)% in the rapid component (IKr) and 45(5)% in the slow component (IKs) of IK. Exposure of the cells to 5 microM forskolin or 100 nM isoprenaline reduced both these effects of cromakalim: with forskolin, the holding current increased by 59(17)%, IKr was reduced by 9(3)%, and IKs by 23(3)%; with isoprenaline, the holding current increased by 100(36)%, IKr was not significantly changed, and IKs was reduced by 27(5)%. With 10 microM glibenclamide present, the only significant effect of cromakalim was reduction of IKs [by 11(3)%].
Cromakalim caused decreases in both components of IK which developed in parallel with activation of IK(ATP). The observations that forskolin, isoprenaline, or glibenclamide all reduced the effects of cromakalim on both IK and IK(ATP) may result from separate effects on the two channel pathways, but are also consistent with the single hypothesis that cromakalim induces an interconversion of potassium channels which is reduced when potassium channels are modified by these three drugs.
本研究旨在探讨克罗卡林激活三磷酸腺苷敏感性钾通道对豚鼠心室肌细胞延迟整流钾电流（IK）的影响。实验分别在不存在和存在福斯高林或异丙肾上腺素以促进IK磷酸化的情况下进行，以及在存在格列本脲以阻断三磷酸腺苷敏感性钾电流（IK(ATP)）的情况下进行。
从豚鼠心室分离单个细胞。在电压钳制条件下研究钾电流。延迟整流电流通过在去极化至+40 mV后复极化至-40 mV的保持电位时的外向尾电流来测量。IK(ATP)的诱导通过保持电流的变化来指示。
暴露于20微摩尔克罗卡林导致保持电流显著增加244（标准误47）%，同时IK的快速成分（IKr）和慢速成分（IKs）分别下降22（5）%和45（5）%。细胞暴露于5微摩尔福斯高林或100纳摩尔异丙肾上腺素可降低克罗卡林的这两种作用：使用福斯高林时，保持电流增加59（17）%，IKr降低9（3）%，IKs降低23（3）%；使用异丙肾上腺素时，保持电流增加100（36）%，IKr无显著变化，IKs降低27（5）%。在存在10微摩尔格列本脲的情况下，克罗卡林的唯一显著作用是降低IKs[降低11（3）%]。
克罗卡林导致IK的两个成分均下降，这与IK(ATP)的激活同时发生。福斯高林、异丙肾上腺素或格列本脲均降低克罗卡林对IK和IK(ATP)的作用，这一观察结果可能源于对两种通道途径的单独作用，但也与单一假设一致，即克罗卡林诱导钾通道的相互转化，而当钾通道被这三种药物修饰时这种转化会减少。
