Block of Lens and Neuronal Gap Junctions by Quinine

奎宁阻断晶状体和神经元间隙连接

• 批准号: 6698790
• 负责人: Miduturu Srinivas
• 金额: $ 20.67万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6698790
• 关键词: acid base balance; analog; binding sites; chemical structure function; computer data analysis; electrophysiology; gap junctions; ion channel blocker; lens; mathematical model; membrane channels; neurons; quinine; site directed mutagenesis; stereochemistry

Gap junction channels provide pathways of intercellular communication=, allowing the passage of ions and small molecules up to 1 kDa in mass or 10-14 nm in diameter. In mammalian and other vertebrate cells, gap junction channels are composed of a family of protein molecules known as connexins. Determination of the roles of channels formed by various connexins is an ongoing area of investigation. One problem with studying gap junction channels is the lack of blockers that are specific and selective. The lack of naturally occurring blockers has in part been attributed to the inaccessibility of gap junctions to extracellular space and the large pore size of these channels. We recently discovered that quinine, a small naturally occurring compound, has significant effects on gap junction channels formed of certain connexins at concentrations comparable to its effect on other cellular processes. The experiments proposed in this project will enable us to understand the mechanism of action of quinine and molecular basis for its action on gap junction channels. These studies combined with future structure-activity studies may lead to the identification or synthesis of a blocking agent that is highly specific for gap junction channels.

间隙连接通道提供细胞间通讯的途径，允许质量高达1 kDa或直径为10-14 nm的离子和小分子通过。在哺乳动物和其他脊椎动物细胞中，间隙连接通道由称为连接蛋白的蛋白质分子家族组成。确定各种连接蛋白形成的通道的作用是一个正在进行的研究领域。研究缝隙连接通道的一个问题是缺乏特异性和选择性的阻断剂。天然存在的阻断剂的缺乏部分归因于间隙连接到细胞外空间的不可接近性和这些通道的大孔径。我们最近发现，奎宁，一个小的天然化合物，有显着的影响，在某些连接蛋白形成的间隙连接通道的浓度与其对其他细胞过程的影响。本计画所提出的实验将使我们了解奎宁的作用机制及其对间隙连接通道作用的分子基础。这些研究结合未来的结构-活性研究可能会导致识别或合成的阻断剂，是高度特异性的间隙连接通道。