Role of the Na+-activated K+ channel Slack (Slo2.2) for cell survival upon ischemic stroke and myocardial infarction

Na 激活的 K 通道 Slack (Slo2.2) 对缺血性中风和心肌梗死细胞存活的作用

• 批准号: 354137032
• 负责人: Professor Dr. Robert Lukowski
• 金额: --
• 依托单位: Pharmazeutisches Institut
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/354137032?language=en
• 关键词: Role; Na+; activated; K+; channel

The Na+-activated K+ channel Slack (Slo2.2) is a member of the Slo gene family predominantly expressed in excitable cells such as neurons and cardiomyocytes. Since large increases in [Na+]i are needed to activate Slack, its roles in physiology and pathophysiology in vivo are still controversially discussed. We suggest that Slack, via K+ outward currents that stabilize the membrane potential, protects from cytotoxic Ca2+overload in neurons and cardiomyocytes under hypoxia and ischemia, known to elicit sharp increases in [Na+]i. To test this hypothesis in vivo we have generated Slack knockout mouse lines. Herein, we will study global and tissue-specific Slack mutants for their susceptibilities towards ischemic damages in brain and heart. We aim to an evaluation of this K+ channel as drug target for prevention and therapy of myocardial infarction and stroke.

Na+激活的K+通道Slack(Slo2.2)是Slo基因家族的成员，主要在神经元和心肌细胞等兴奋性细胞中表达。由于激活Slack需要大量增加[Na+]i，其在体内的生理学和病理生理学中的作用仍有争议。我们认为，Slack通过K+外向电流稳定膜电位，保护神经元和心肌细胞免受缺氧和缺血条件下细胞毒性钙超载的影响，已知的是引起[Na+]i急剧增加。为了在体内验证这一假说，我们建立了Slack基因敲除小鼠系。在这里，我们将研究全局和组织特异性Slack突变体对脑和心脏缺血损伤的易感性。我们的目标是评价这种K+通道作为预防和治疗心肌梗死和中风的药物靶点。