ATP -a mediator of central chemoreception in brain stem

ATP - 脑干中枢化学感受的介质

• 批准号: G0500198/1
• 负责人: Nicholas Dale
• 金额: $ 40.56万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0500198%2F1
• 关键词: ATP; mediator; central; chemoreception; brain

Without a mechanical aid, it is impossible to stop breathing by will power. Why? Because the levels of CO2 in inspired air and in blood are an extremely powerful drive to breathe ?if these levels go up (as they would during self-willed asphyxiation or re-breathing from a plastic bag) we breathe more powerfully and rapidly. Specialized areas of the brain stem have long been known to detect CO2 in brain and relay this information to the neural networks that control breathing. Despite this, the detailed mechanisms of CO2 detection (chemoreception), and indeed the chemosensory cells themselves remain unknown. We have recently made a breakthrough in discovering that ATP is released from these specialized areas of the brain stem during elevated CO2 and is an essential link in the chemosensory reflex. We shall now exploit this finding by using experimentally simpler in vitro preparations of the brain stem. We shall look at the mechanisms of ATP release, as these will lead us to a fundamental understanding of the mechanisms of chemoreception. Thus we shall produce detailed maps of the locations of ATP release. We shall look at the characteristics of ATP release, which may highlight the types of cells that release ATP during elevated CO2. We shall identify the ion channels within the chemosensory cells responsible for detecting changes in CO2 and ultimately causing the release of ATP. Finally we shall examine release from of ATP from isolated cells in response to CO2 to allow us to identify them.

没有机械辅助，靠意志力是不可能停止呼吸的。为什么？为什么？因为吸入的空气和血液中的二氧化碳水平是呼吸的一个非常强大的动力？如果这些水平上升（就像他们在自愿窒息或从塑料袋中重新呼吸时一样），我们呼吸得更有力和更快。长期以来，脑干的专门区域一直被认为可以检测大脑中的二氧化碳，并将此信息传递给控制呼吸的神经网络。尽管如此，CO2检测（化学感受）的详细机制以及化学感受细胞本身仍然未知。我们最近取得了突破性进展，发现ATP在CO2升高时从脑干的这些专门区域释放出来，并且是化学感觉反射的重要环节。我们现在将利用这一发现，通过实验上更简单的脑干体外制备。我们将研究ATP释放的机制，因为这些将使我们对化学感受机制有一个基本的了解。因此，我们将绘制ATP释放位置的详细地图。我们将研究ATP释放的特征，这可能会突出在CO2升高期间释放ATP的细胞类型。我们将确定负责检测CO2变化并最终导致ATP释放的化学感受细胞内的离子通道。最后，我们将检查从ATP的释放从孤立的细胞响应CO2，使我们能够识别它们。