STRUCTURE OF POTASSIUM CHANNELS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们在NECAT的研究旨在破译各种真核钾离子通道的门控机制和药理学特性。第一个通道是电压依赖的K通道，它响应膜电压的变化而开放，负责在脑细胞中产生电信号。我们的目标是确定中间门控状态的结构，以了解膜电压如何驱动闭合构象和开放构象之间的通道。第二个通道是真核细胞的内向整流钾通道，它控制着许多神经元的静息膜电位。第三个通道是G蛋白门控通道，它响应G蛋白信号通路的刺激而开放。这种通道类型在其他过程中调节心率，是治疗心房颤动的重要潜在靶点。第四个通道是高电导钙通道和电压依赖性钾通道。该通道在多种类型的细胞中发挥作用，包括血管和呼吸道平滑肌。它是治疗高血压和哮喘的潜在靶点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our research at NECAT aims to decipher the gating mechanisms and pharmacological properties of various eukaryotic K+ ion channels. The first channel is the voltage-dependent K+ channel, which opens in response to changes in membrane voltage and is responsible for producing electrical signals in brain cells. We are aiming to determine structures of intermediate gating states to understand how membrane voltage drives the channel between closed and opened conformations. The second channel is the eukaryotic inward rectifier K+ channel, which controls the resting membrane potential in many neurons. The third channel is the G-protein-gated channel, which opens in response to the stimulation of G-proteins signaling pathways. This channel type regulates heart rate, among other processes, and is an important potential target for the treatment of atrial fibrillation. The fourth channel is the high-condcutance Ca2+and voltage-dependent K+ channel. This channel functions in various cell types, including vascular and airway smooth muscle. It is a potential target for the treatment of hypertension and asthma.