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）是Slo基因家族的成员，主要表达于神经元和心肌细胞等可兴奋细胞中。由于激活Slack需要大量增加[Na+]i，因此其在体内生理和病理生理中的作用仍存在争议。我们认为，Slack通过稳定膜电位的K+向外电流，在缺氧和缺血情况下保护神经元和心肌细胞免受细胞毒性Ca2+过载的影响，已知这会引起[Na+]i的急剧增加。为了在体内验证这一假设，我们产生了Slack敲除小鼠系。在此，我们将研究全局和组织特异性Slack突变体对脑和心脏缺血性损伤的易感性。我们的目的是评估这种K+通道作为预防和治疗心肌梗死和中风的药物靶点。

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.