Leak potassium channels in chemosensitive RTN neurons

描述（由申请人提供）：中枢化学感受，即大脑感知CO2/pH并调节呼吸的机制，被认为涉及后斜方核（RTN）内延髓腹侧表面的神经元。然而，这些RTN化学感受器的细胞特性和分子机制是未知的。最近，我们鉴定了一群CO2敏感性RTN，其可能是难以捉摸的RTN化学受体;即，广泛的表面树突，是神经元能的，直接投射到呼吸中枢。在脑切片中，具有类似形态的RTN神经元本质上是pH敏感的，并且表达在静息膜电位下活跃的开放整流pH敏感性K+电流，因此表明pH敏感性背景K+（例如，ASK）有助于RTN神经元的固有pH敏感性。在这项研究中，我使用电生理技术来确定是否由pH敏感的RTN神经元（具体目标1）和单细胞RT-PCR来确定是否由RTN神经元（具体目标2）制作的Task-like电流。这些实验的结果将确定是否存在pH敏感的RTN神经元的任务电流，并提供深入了解化学感受机制的细胞机制。

DESCRIPTION (provided by applicant): Central chemoreception, the mechanism by which the brain senses CO2/pH and regulates breathing, is thought to involve neurons on the ventral surface of the medulla oblongata within the retrotrapezoid nucleus (RTN). However, the cellular identity and molecular mechanism of these RTN chemoreceptors is unknown. Recently we identified a population of CO2-sensitive RTN that may be the elusive RTN chemoreceptors; i.e., extensive superficial dendrites, are glutamatergic and project directly to respiratory centers. In the brain slice, RTN neurons with a similar morphology are intrinsically pH-sensitive and express an open rectifying pH-sensitive K+ current that is active at resting membrane potential, thus suggesting that a pH-sensitive background K+ (e.g., TASK) contributes to intrinsic pH sensitivity of RTN neurons. In this research proposal I use electrophysiological techniques to determine if a TASK-like current is expressed by pH sensitive RTN neurons (Specific Aim 1) and single cell RT-PCR to determine if TASK mRNA transcripts are made by RTN neurons (Specific Aim 2). Results from these experiments will determine if TASK currents are present in pH-sensitive RTN neurons and provide insight into the cellular mechanism of mechanism chemoreception.