Department of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Molecular Neurogenetics, Center of Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Physiol. 2018 Mar 1;596(5):769-783. doi: 10.1113/JP275477. Epub 2018 Feb 6.
Mammalian ether-à-go-go (EAG) channels are voltage-gated K channels. They are encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10), erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes are expressed in the brain where they effectively modulate neuronal excitability. This Topical Review describes the biophysical properties of each of the EAG channel subtypes, their function in neurons and the neurological diseases induced by EAG channel mutations. In contrast to the function of erg currents in the heart, where they contribute to repolarization of the cardiac action potential, erg currents in neurons are involved in the maintenance of the resting potential, setting of action potential threshold and frequency accommodation. They can even support high frequency firing by preventing a depolarization-induced Na channel block. EAG channels are modulated differentially, e.g. eag channels by intracellular Ca , erg channels by extracellular K and GPCRs, and elk channels by changes in pH. So far, only currents mediated by erg channels have been recorded in neurons with the help of selective blockers. Neuronal eag and elk currents have not been isolated due to the lack of suitable channel blockers. However, findings in KO mice indicate a physiological role of eag1 currents in synaptic transmission and an involvement of elk2 currents in cognitive performance. Human eag1 and eag2 gain-of-function mutations underlie syndromes associated with epileptic seizures.
哺乳动物的醚-α--go-go（EAG）通道是电压门控 K 通道。它们由 KCNH 基因家族编码，并分为三个亚家族，即 eag（Kv10）、erg（eag 相关基因；Kv11）和 elk（eag 样；Kv12）。所有 EAG 通道亚型都在大脑中表达，在那里它们有效地调节神经元兴奋性。本专题综述描述了每种 EAG 通道亚型的生物物理特性、它们在神经元中的功能以及由 EAG 通道突变引起的神经疾病。与 erg 电流在心内的功能相反，erg 电流在心内有助于复极化心脏动作电位，erg 电流在神经元内参与维持静息电位、设置动作电位阈值和频率适应。erg 电流甚至可以通过防止去极化诱导的钠通道阻断来支持高频放电。EAG 通道被不同地调节，例如，eag 通道被细胞内 Ca 调节，erg 通道被细胞外 K 和 GPCR 调节，elk 通道被 pH 变化调节。到目前为止，只有在选择性阻滞剂的帮助下，才能在神经元中记录到由 erg 通道介导的电流。由于缺乏合适的通道阻滞剂，神经元中的 eag 和 elk 电流尚未被分离。然而，KO 小鼠的研究结果表明 eag1 电流在突触传递中具有生理作用，elk2 电流参与认知表现。人类的 eag1 和 eag2 功能获得性突变是与癫痫发作相关的综合征的基础。
