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Modulation Of Fast And Slow Inactivation In Two Cardiac Nav Channel Isoforms By Sdz 211-939, Tyce Jeffrey Kearl
Modulation Of Fast And Slow Inactivation In Two Cardiac Nav Channel Isoforms By Sdz 211-939, Tyce Jeffrey Kearl
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Here we report a hitherto unknown effect of a synthetic inactivation inhibitor on inactivation in cardiac sodium channels (Nav1.5) from two different species: human and bovine. SDZ 211-93 9 stabilized the slow inactivated-state in both channels as seen by an increased steady-state probability of slow inactivation. SDZ also destabilized the fast-inactivated state and increased the amplitude of persistent currents. SDZ modulated conductance parameters, open-state fast inactivation time constants, and activation kinetics of hNav1.5, but not bNav1.5. These findings will aid future studies designed to elucidate the binding site and molecular mechanisms of inactivation inhibitors …