Relating the binding of single ligands to activation in single HCN and CNG channels (A05)

将单个配体的结合与单个 HCN 和 CNG 通道中的激活联系起来 (A05)

• 批准号: 279182658
• 金额: --
• 依托单位: Institut für Physiologie II - Herz-Kreislauf-Physiologie
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/279182658?language=en
• 关键词: Relating; binding; single; ligands; activation

The interactions of single labeled cGMP and cAMP molecules will be studied in CNGA2 and HCN2 ion channels. To achieve this at high nanomolar concentrations, the channels will be studied in either supported native membranes placed in an evanescent field or in excised membrane patches positioned at the tip of patch pipettes with sub-diffraction dimensions to record single-channel currents in parallel. To optimize these methods novel cGMP and cAMP derivatives will be designed in silico, synthesized and characterized. The observations will be analyzed in terms of hidden Markov models to refine our understanding of the channel dynamics.

单标记cGMP与cAMP分子在CNGA_2和HCN_2离子通道中的相互作用将被研究。为了在高纳米分子浓度下实现这一点，将在放置在消失场中的支持的自然膜中或在位于亚衍射尺寸的贴片顶端的离体膜贴片中研究通道，以平行记录单通道电流。为了优化这些方法，将在电子计算机上设计、合成和表征新的cGMP和cAMP衍生物。观测结果将根据隐马尔可夫模型进行分析，以完善我们对信道动力学的理解。