CHEMICAL TRANSDUCTION & MODULATION OF CHANNEL CURRENTS

化学传导

• 批准号: 3216712
• 负责人: ROBERT J O'CONNELL
• 金额: $ 15.65万
• 依托单位: WORCESTER FOUNDATION FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-25 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3216712
• 关键词: action potentials; biochemistry; biological signal transduction; biophysics; chemoreceptors; dendrites; electron microscopy; electrophysiology; medial olfactory area; membrane channels; membrane proteins; neural information processing; olfactions; pheromone; phospholipids; radioassay; second messengers; sensory feedback; single cell analysis

The incessant flow of chemical signals between and among the individual neural elements of the brain is widely acknowledged to be an essential determinant of higher neural function. Therefore the physiological mechanisms which underlie the ability of primary olfactory receptor neurons to detect, transduce and process chemical signals must provide a good model for these processes elsewhere in the brain. Individual olfactory receptor neurons respond to multiple chemical stimuli and differ dramatically in the particular array of effective odorants and in the relative amounts of each required to elicit a significant change in action potential production. In receptor neurons, most receptor sites, second messenger systems and single current channels are thought to be integral plasma membrane proteins. Thus, the complexity seen in olfactory receptor neurons can be ascribed to differences in the kind, number, distribution, activation and interaction among these individual proteins. Activation of receptor sites is presumed to stimulate or modulate in some way, perhaps through a second messenger mechanism, various ionic currents which flow through the integral membrane channels. These brief individual currents, in concert, ultimately result in sufficient transmembrane current flow to generate a propagated action potential. In these experiments fragments of insect olfactory receptor neuron dendrites will be reconstituted in phospholipid bilayers on the tips of patch electrodes in order to explore the biophysics of olfactory transduction, signal amplification and current flow. The questions to be asked include: 1) Does an individual odor interact with more than one kind of receptor site? 2) Are there different kinds of receptor sites on single olfactory receptor neurons? 3) If there are, how many kinds are there and how do they differ in their individual binding properties? 4) Does the activation of one type of receptor site influence the activation of another? 5) How are these receptor sites coupled to the activation of single channel currents? 6) Do effective odors modulate single channel currents directly, or indirectly through a second messenger system? 7) If second messenger systems are involved, how are they modulated and regulated? 8) Are particular types of receptor sites always associated with a particular type of channel or second messenger system? 9) How many different types of individual channel currents are there? 10) How do channels vary in their ionic requirements and voltage dependence? Answers to these questions will aid in our understanding of brain function.

化学信号在不同区域之间的不断流动 人们普遍认为，大脑中的单个神经元素 是高级神经功能的重要决定因素。因此 形成这种能力的生理机制 初级嗅觉感受器神经元的检测、转导和 过程化学信号必须为这些提供一个好的模型 大脑中其他地方的过程。个体嗅觉感受器 神经元对多种化学刺激的反应不同 在特定的有效香料阵列中戏剧性地 每一项的相对数量都需要引起显著的 动作电位产生的变化。在受体神经元中，大多数 受体部位、第二信使系统和单电流 通道被认为是完整的质膜蛋白。 因此，在嗅觉感受器神经元中看到的复杂性可以是 归因于种类、数量、分布、 这些单独的蛋白质之间的激活和相互作用。 受体位置的激活被推定为刺激或调节 在某种程度上，也许是通过第二信使机制， 流经整体膜的各种离子流 频道。这些短暂的单独的水流，最终， 导致足够的跨膜电流以产生 传播性动作电位。在这些实验中， 昆虫嗅觉感受器神经元树突将在 贴片电极尖端的磷脂双层膜 探索嗅觉传导、信号传递的生物物理学 放大和电流流动。要问的问题 包括：1)一种气味是否与不止一种气味相互作用 受体的种类？2)有不同种类的受体吗 单个嗅觉感受器神经元上的位置？3)如果有，如何 有很多种，它们的个体有什么不同 结合特性？4)一种受体的激活 网站会影响另一个网站的激活吗？5)这些是如何实现的 与单通道激活偶联的受体位点 电流？有效气味会调制单通道电流吗？ 直接或间接通过第二个信使系统？7)如果 第二信使系统参与其中，它们是如何调节的 和受调控的？8)特定类型的受体位点总是 与特定类型的通道或第二信使相关联 系统？有多少种不同类型的单独频道 有电流吗？通道的离子是如何变化的 要求和电压依赖关系？这些问题的答案 提问将有助于我们对大脑功能的理解。