Kiehn J, Lacerda A E, Wible B, Brown A M
Rammelkamp Center for Research, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.
Circulation. 1996 Nov 15;94(10):2572-9. doi: 10.1161/01.cir.94.10.2572.
The human ether-a-go-go-related gene (HERG) is one locus for the hereditary long-QT syndrome. A hypothesis is that HERG produces the repolarizing cardiac potassium current IKr with the consequence that mutations in HERG prolong the QT interval by reducing IKr. The elementary properties of HERG are unknown, and as a test of the hypothesis that HERG produces IKr, we compared their elementary properties.
We injected HERG cRNA into Xenopus oocytes and measured currents from single channels or current variance from the noise produced by ensembles of channels recorded from macro patches. Single-channel conductance was dependent on the extracellular potassium concentration ([K]o). At physiological [K]o, it was 2 picosiemens (pS), and at 100 mmol/L [K]o, it was 10 pS. Openings occurred in bursts with a mean duration of 26 ms at -100 mV. Mean open time was 3.2 ms and closed times were 1.0 and 26 ms. In excised macro patches, HERG currents were blocked by the class III antiarrhythmic drug dofetilide, with an IC50 of 35 nmol/L. Dofetilide block was slow and greatly attenuated at positive potentials at which HERG rectifies.
The microscopic physiology of HERG and IKr is similar, consistent with HERG being an important component of IKr. The pharmacology is also similar; dofetilide appears to primarily block activated channels and has a much lower affinity for closed and inactivated channels.
人类醚 - 去极化相关基因（HERG）是遗传性长QT综合征的一个位点。一种假说认为，HERG产生复极化心脏钾电流IKr，因此HERG中的突变通过降低IKr来延长QT间期。HERG的基本特性尚不清楚，作为对HERG产生IKr这一假说的检验，我们比较了它们的基本特性。
我们将HERG cRNA注射到非洲爪蟾卵母细胞中，并测量单通道电流或从宏观膜片记录的通道集合产生的噪声的电流方差。单通道电导取决于细胞外钾浓度（[K]o）。在生理[K]o时，它为2皮西门子（pS），在100 mmol/L [K]o时，它为10 pS。在-100 mV时，开放以爆发形式出现，平均持续时间为26 ms。平均开放时间为3.2 ms，关闭时间为1.0和26 ms。在切除的宏观膜片中，HERG电流被Ⅲ类抗心律失常药物多非利特阻断，IC50为35 nmol/L。多非利特阻断缓慢，且在HERG发生整流的正电位时大大减弱。
HERG和IKr的微观生理学相似，这与HERG是IKr的重要组成部分一致。药理学也相似；多非利特似乎主要阻断激活的通道，对关闭和失活的通道亲和力低得多。
