Regulation of Voltage-gated Proton Channel

摘要 电压门控Hv1质子通道是电压门控离子通道家族的一员，它 在兴奋性和非兴奋性细胞的排酸和调节pH中起关键作用 多种细胞类型的动态平衡。Hv1质子通道提供电荷和pH 吞噬细胞NADPH氧化酶呼吸爆发时的代偿及对照 吞噬细胞中产生的活性氧，它介导了质子在肺中的外流 肺泡细胞膜和酸化过度碱性的呼吸道表面液体在呼吸道细胞。 Hv1是精子鞭毛细胞内pH的调节者，在精子中起着至关重要的作用。 获能。此外，Hv1活性是酸排出形成动作电位所必需的。 蜗牛神经元。研究表明，Hv1通道的生物物理特性和功能 在各种组织中都不相同，天然电压门控质子的不同表现 不同细胞类型中的通道表明存在调制Hv1的调制伙伴 质子通道的功能。我们最近确定了一个跨膜蛋白家族为Hv1 频道互动演员。我们发现跨膜蛋白的存在改变了Hv1 通道的活动，并调节通道的电压依赖门控。这样做的目的是 一项旨在确定跨膜蛋白对Hv1通道的影响的提案 生理学、生物物理学和药理学。拟议的研究将建立生理学 跨膜调节剂对Hv1通道调控的相关性及对新发现的启示 电压门控离子通道调节机制。

Abstract The voltage-gated Hv1 proton channel is a member of voltage-gated ion channel family, it plays a key role in the acid extrusion from excitable and non-excitable cells and regulate pH homeostasis in a variety of cell types. The Hv1 proton channel provides charge and pH compensation during the respiratory burst of the phagocyte NADPH oxidase and controls production of reactive oxygen species in phagocytes, it mediates proton efflux at the pulmonary alveolar cell membrane and acidifies excessively alkaline airway surface liquid in the airway cells. Hv1 is found to be a sperm flagellar regulator of intracellular pH, and play a crucial role in sperm capacitation. In addition, Hv1 activity is required for acid extrusion to shape action potentials in snail neurons. Studies have shown that biophysical properties and functions of the Hv1 channel are not identical in a variety of tissues, the distinct manifestations of native voltage-gated proton channels in different cell types indicate the existence of modulatory partners modulating the Hv1 proton channel's function. We recently identified a family of transmembrane protein as the Hv1 channel interactor. We discovered that the presence of the transmembrane protein alters the Hv1 channel's activity and modulates the channel's voltage-dependent gating. The goal of this proposal is designed to determine the effects of the transmembrane protein on the Hv1 channel physiology, biophysics, and pharmacology. The proposed research will establish the physiological relevance of Hv1 channel regulation by transmembrane modulators and shed light on novel voltage-gated ion channel regulatory mechanisms.