Regulation of HERG proteins by chemical chaperones

描述(申请人提供)：该项目的长期目标是研究药物对无法正常进入质膜的离子通道的挽救作用。蛋白质转运的失败是先天性长QT2综合征(LQT2)相关离子通道病变的基础。与高亲和力离子通道结合的药物可以修复突变离子通道的转运缺陷。然而，这些渠道的药物救援机制仍然知之甚少。这项建议从分子和功能水平上考察了长QT2转运缺陷在药理挽救方面的差异。

DESCRIPTION (provided by applicant): The long-term goal of this project is to investigate the pharmacological rescue of ion channels that fail to traffic normally to the plasma membrane. Failure of protein trafficking underlies ion channelopathies associated with congenital Long QT2 syndrome (LQT2). Drugs that bind to channels with a high affinity can restore the trafficking defects of mutant ion channels. However, the mechanisms that underlie the drug rescue of these channels remain poorly understood. This proposal examines the differences in pharmacological rescue of Long QT2 trafficking defects at the molecular and functional level.