Molecular Biology and Physiology of Neuronal Modulation

有许多递质物质调节中枢神经系统神经细胞的活动。这项建议的目的是阐明这些递质物质激活细胞内信使过程的机制，这些信使过程通过它们对钾通道电导的作用而导致兴奋性的调节。最近的研究表明，神经元的兴奋性依赖于钾通道，钾通道又受称为GI和GO的G蛋白调节，G蛋白有几种亚型。这项研究的具体目的是确定哪些G蛋白亚型与神经递质作用(乙酰胆碱和生长抑素)有关。分子生物学技术将被用来产生特定的突变，选择性地灭活G蛋白，从而确定它们中的哪一个直接受到神经递质的影响，从而作用于细胞的钾电导。为此，突变的阿尔法亚基将被插入到AtT-20细胞中，AtT-20是一种含有G蛋白调节的钾通道的垂体瘤细胞系。然后可以确定突变体对钾通道功能的影响。

There are many transmitter substances which regulate the activity of nerve cells of the central nervous system. The objective of this proposal is to elucidate the mechanisms by which these transmitter substances activate intracellular messenger processes that lead to the modulation of excitability through their action on potassium channel conductance properties. Recent studies have shown that excitability of neurons is dependent on potassium channels which are, in turn, regulated by G-proteins called Gi and Go, of which there are several subtypes. The specific aim of this investigation is to identify which of the G-protein subtypes are related to neurotransmitter action (acetylcholine and somatostatin). Molecular biological techniques will be used to produce specific mutations to selectively inactivate G-proteins and thereby determine which of them is directly affected by the neurotransmitters to act on potassium conductance of the cell. For this purpose mutated alpha subunits will be inserted into AtT-20 cells, a pituitary tumor cell line which contain G-protein regulated potassium channels. The effect of the mutants can then be ascertained on potassium channel function.