Wymore R S, Gintant G A, Wymore R T, Dixon J E, McKinnon D, Cohen I S
Department of Physiology and Biophysics, State University of New York at Stony Brook 11794, USA.
Circ Res. 1997 Feb;80(2):261-8. doi: 10.1161/01.res.80.2.261.
The human K+ channel gene, HERG, has been linked to the type 2 form of the autosomal dominant long-QT syndrome and has been suggested to encode the fast component of the delayed rectifier K+ current (IKr) found in heart. To date, the published electrophysiological and pharmacological data on the Xenopus-expressed HERG are very similar but are not identical to those of the endogenous IKr. In an effort to provide a different type of correlative data on the relationship between erg and IKr. cDNA fragments of erg homologues from guinea pig, rabbit, human, dog, and rat were cloned and used to test for the presence of erg mRNA in cardiac tissue. RNase protection assays reveal that erg message is found in the hearts of all five species and that it is expressed uniformly throughout the heart. The erg transcript is expressed at relatively high levels, being approximately 50% more abundant than the most prevalent Kv-class K+ channel transcript in canine ventricle (Kv4.3) erg transcripts were found to have a wide tissue distribution in rat and are abundant in the brain, retina, thymus, and adrenal gland and are also found in skeletal muscle, lung, and cornea. Since there were no published reports of an IKr-like current in the rat heart, electrophysiological studies were performed to test whether the significant level of erg message in rat heart was correlated with the presence of an IKr-like current in rat. In isolated rat ventricular myocytes, an E-4031-sensitive current was observed, which is consistent with the presence of IKr. These results strengthen the link between erg and the native IKr in heart and suggest that erg may play an important role in other noncardiac tissues.
人类钾离子通道基因HERG与常染色体显性长QT综合征2型有关，有人提出它编码心脏中发现的延迟整流钾电流（IKr）的快速成分。迄今为止，已发表的关于非洲爪蟾表达的HERG的电生理和药理学数据非常相似，但与内源性IKr的数据并不完全相同。为了提供关于erg与IKr之间关系的另一种相关数据，克隆了豚鼠、兔子、人类、狗和大鼠的erg同源物的cDNA片段，并用于检测心脏组织中erg mRNA的存在。核糖核酸酶保护分析表明，在所有这五个物种的心脏中都发现了erg信息，并且它在整个心脏中均匀表达。erg转录本以相对较高的水平表达，比犬心室中最普遍的Kv类钾离子通道转录本（Kv4.3）丰富约50%。erg转录本在大鼠中具有广泛的组织分布，在脑、视网膜、胸腺和肾上腺中丰富，在骨骼肌、肺和角膜中也有发现。由于没有关于大鼠心脏中类似IKr电流的已发表报告，因此进行了电生理研究，以测试大鼠心脏中erg信息的显著水平是否与大鼠中类似IKr电流的存在相关。在分离的大鼠心室肌细胞中，观察到一种对E-4031敏感的电流，这与IKr的存在一致。这些结果加强了erg与心脏中天然IKr之间的联系，并表明erg可能在其他非心脏组织中起重要作用。
