Trudeau M C, Titus S A, Branchaw J L, Ganetzky B, Robertson G A
Department of Physiology, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53706, USA.
J Neurosci. 1999 Apr 15;19(8):2906-18. doi: 10.1523/JNEUROSCI.19-08-02906.1999.
Members of the Ether à go-go (Eag) K+ channel subfamilies Eag, Erg, and Elk are widely expressed in the nervous system, but their neural functions in vivo remain largely unknown. The biophysical properties of channels from the Eag and Erg subfamilies have been described, and based on their characteristic features and expression patterns, Erg channels have been associated with native currents in the heart. Little is known about the properties of channels from the Elk subfamily. We have identified a mouse gene, Melk2, that encodes a predicted polypeptide with 48% amino acid identity to Drosophila Elk but only 40 and 36% identity with mouse Erg (Merg) and Eag (Meag), respectively. Melk2 RNA appears to be expressed at high levels only in brain tissue. Functional expression of Melk2 in Xenopus oocytes reveals large, transient peaks of current at the onset of depolarization. Like Meag currents, Melk2 currents activate relatively quickly, but they lack the nonsuperimposable Cole-Moore shift characteristic of the Eag subfamily. Melk2 currents are insensitive to E-4031, a class III antiarrhythmic compound that blocks the Human Ether-à-go-go-Related Gene (HERG) channel and its counterpart in native tissues, IKr. Melk2 channels exhibit inward rectification because of a fast C-type inactivation mechanism, but the slower rate of inactivation and the faster rate of activation results in less inward rectification than that observed in HERG channels. This characterization of Melk currents should aid in identification of native counterparts to the Elk subfamily of channels in the nervous system.
Ether à go-go（Eag）钾离子通道亚家族Eag、Erg和Elk的成员在神经系统中广泛表达，但其在体内的神经功能仍 largely未知。已描述了Eag和Erg亚家族通道的生物物理特性，基于其特征和表达模式，Erg通道已与心脏中的天然电流相关联。关于Elk亚家族通道的特性知之甚少。我们鉴定了一个小鼠基因Melk2，它编码一种预测的多肽，与果蝇Elk的氨基酸同一性为48%，但与小鼠Erg（Merg）和Eag（Meag）的同一性分别仅为40%和36%。Melk2 RNA似乎仅在脑组织中高水平表达。Melk2在非洲爪蟾卵母细胞中的功能性表达揭示了去极化开始时电流的大的瞬时峰值。与Meag电流一样，Melk2电流激活相对较快，但它们缺乏Eag亚家族特有的不可叠加的科尔 - 摩尔偏移特征。Melk2电流对E - 4031不敏感，E - 4031是一种III类抗心律失常化合物，可阻断人类醚 - 去极化相关基因（HERG）通道及其在天然组织中的对应物IKr。由于快速的C型失活机制，Melk2通道表现出内向整流，但失活速率较慢和激活速率较快导致内向整流比HERG通道中观察到的要少。对Melk电流的这种表征应有助于识别神经系统中Elk通道亚家族的天然对应物。
