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.

没有机械援助，就不可能通过意志力停止呼吸。为什么？因为受启发的空气和血液中的二氧化碳水平是呼吸的极大动力？如果这些水平上升（就像它们在塑料袋中自我杀害或重新呼吸时一样），我们会更加有力，快速地呼吸。长期以来，已知脑干的专业区域可以检测到大脑中的二氧化碳，并将这些信息传递给控制呼吸的神经网络。尽管如此，二氧化碳检测的详细机制（化学感受），实际上化学感应细胞本身仍然未知。最近，我们在发现二氧化碳升高期间从脑干的这些专业区域释放ATP取得了突破，这是化学感应反射的重要环节。现在，我们将通过使用实验更简单的脑干制剂来利用这一发现。我们将研究ATP释放的机制，因为这些机制将使我们对化学感受的机制有基本的理解。因此，我们将制作ATP释放位置的详细地图。我们将研究ATP释放的特征，该特征可能会突出二氧化碳期间释放ATP的细胞类型。我们将确定负责检测二氧化碳变化并最终导致ATP的变化的化学感应细胞内的离子通道。最后，我们将检查ATP从孤立细胞中释放的响应，以响应CO2，以使我们能够识别它们。