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
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