Leak potassium channels in chemosensitive RTN neurons

描述（由申请人提供）：中枢化学接受是大脑感知二氧化碳/pH值并调节呼吸的机制，被认为与后梯形核（RTN）内延髓腹侧表面的神经元有关。然而，这些RTN化学受体的细胞身份和分子机制尚不清楚。最近，我们发现了一个对二氧化碳敏感的RTN群体，可能是难以捉摸的RTN化学受体；也就是说，广泛的浅表树突是谷氨酸能的，直接投射到呼吸中枢。在脑片中，具有相似形态的RTN神经元本质上是pH敏感的，并表达一个开放的整流pH敏感K+电流，该电流在静息膜电位下活跃，从而表明pH敏感背景K+（例如TASK）有助于RTN神经元的内在pH敏感性。在本研究计划中，我使用电生理技术来确定pH敏感的RTN神经元是否表达TASK样电流（Specific Aim 1），并使用单细胞RT-PCR来确定RTN神经元是否产生TASK mRNA转录本（Specific Aim 2）。这些实验的结果将确定TASK电流是否存在于ph敏感的RTN神经元中，并为机制化学接受的细胞机制提供见解。

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.