Tissue and species distribution of mRNA for the I-Kr-like K+ channel, erg
Tissue and species distribution of mRNA for the I-Kr-like K+ channel, erg
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DOI：
10.1161/01.res.80.2.261
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发表时间：
1997-02-01
影响因子：
20.1
通讯作者：
Cohen, IS
中科院分区：
文献类型：
--
作者：
Wymore, RS;Gintant, GA;Cohen, IS
人类 K+ 通道基因 HERG 与 2 型常染色体显性长 QT 综合征有关，并被认为编码心脏中发现的延迟整流 K+ 电流 (I-Kr) 的快速成分。迄今为止，已发表的非洲爪蟾表达的 HERG 的电生理学和药理学数据与内源 I-Kr 的电生理学和药理学数据非常相似，但并不完全相同。为了提供关于 erg 和 I-Kr 之间关系的不同类型的相关数据，我们克隆了来自豚鼠、兔子、人、狗和大鼠的 erg 同源物的 cDNA 片段，并用于测试心脏组织中是否存在 erg mRNA。 RNase 保护测定表明，erg 信息存在于所有五个物种的心脏中，并且在整个心脏中均匀表达。 erg 转录本的表达水平相对较高，比犬心室中最常见的 Kv 类 K+ 通道转录本 (Kv4.3) 丰富约 50%。 erg 转录本被发现在大鼠体内具有广泛的组织分布，在大脑、视网膜、胸腺和肾上腺中含量丰富，并且在骨骼肌、肺和角膜中也有发现。由于尚未发表关于大鼠心脏中 I-Kr 样电流的报道，因此进行了电生理学研究，以测试大鼠心脏中 erg 信息的显着水平是否与大鼠中 I-Kr 样电流的存在相关。在离体大鼠心室肌细胞中，观察到 E-4031 敏感电流，这与 I-Kr 的存在一致。这些结果加强了 erg 与心脏中天然 I-Kr 之间的联系，并表明 erg 可能在其他非心脏组织中发挥重要作用。
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 (I-Kr) 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 I-Kr. In an effort to provide a different type of correlative data on the relationship between erg and I-Kr, cDNA fragments of erg homologues from guinea pig, rabbit, human, dog, and rat wen 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 approximate to 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 I-Kr-like current in the rat heart, electrophysiological studies were performed to test whether the significant lever of erg message in rat heart was correlated with the presence of an I-Kr-like current in rat. In isolated rat ventricular myocytes, an E-4031-sensitive current was observed, which is consistent with the presence of I-Kr. These results strengthen the link between erg and the native I-Kr in heart and suggest that erg may play an important role in other noncardiac tissues.