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

• Applicants: Professor Dr. Robert Lukowski; Professor Dr. Peter Ruth
• Subject Area: Pharmacology
• Term: from 2017 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 354137032

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.

• DFG Programme: Research Grants