Functional and structural dynamics of KCNH4 and KCNH8

摘要 离子通道是大脑和心脏所有电兴奋性和离子缺陷的基础。 经络是许多人类疾病的原因。KCNH系列通道、ERG、 麋鹿和EAG都是电压依赖性钾通道，专为它们的 在塑造细胞电活动方面的作用。KCNH通道中的缺陷已经被 被证明与认知缺陷、精神分裂症风险增加、心脏病 心律失常和癌症。鉴于它们的重要性，令人惊讶的是，一些KCNH 家庭成员被认为是“未被充分研究的”。这项建议的目标是研究 未被研究的KCNH4和KCNH8通道的功能和结构动力学 为未来研究这些通道在人类中的潜在作用奠定了基础 健康和疾病。在此之前，我们已经执行了许多结构和功能 KCNH及相关渠道的实验和发明突破性的新技术 使我们能够完整地记录分子重排的荧光方法 与电生理记录同步的通道。我们建议将这些应用于 测定KCNH4和KCNH8功能和结构动力学的方法 频道。这些实验将导致第一幅未被研究的动态图景 频道。

Abstract Ion channels underlie all electrical excitability in the brain and heart, and defects in ion channels are the cause of many human disorders. The KCNH family of channels, ERG, ELK, and EAG, are voltage-dependent potassium channels that are specialized for their role in shaping the electrical activity of cells. Defects in KCNH channels have been shown to be linked to cognitive defects, increased risk of schizophrenia, cardiac arrhythmias, and cancer. Given their importance, it is surprising that some of the KCNH family members are considered “understudied”. The goal of this proposal is to study the functional and structural dynamics of the understudied KCNH4 and KCNH8 channels to lay the groundwork for future studies on the potential role of these channels in human health and disease. Previously we have performed many structural and functional experiments on KCNH and related channels and invented ground-breaking new fluorescence methods that allow us to record molecular rearrangements in intact channels simultaneous with electrophysiological recording. We propose to apply these methods to measure the functional and structural dynamics of KCNH4 and KCNH8 channels. These experiments will lead to the first dynamic picture of these understudied channels.