High-throughput screen for identifying channel blockers that selectively distinguish transient from persistent sodium channels

摘要

A method for identifying a Na⁺ channel blocker, including providing a cell containing a Na⁺ channel, demonstrating both a transient and a persistent current. The cell includes a potassium (K⁺) channel and a Na/K ATPase (Na⁺ pump). A fluorescent dye is disposed into the well. The fluorescent dye is sensitive to change in cell membrane potential in order to enable optical measurement of cell membrane potential. A Na⁺ channel blocker, to be identified, is added to the well and a stimulating current is passed through the cell in an amount sufficient to generate an action potential before and after the addition of the Na⁺ channel blocker. Thereafter, a change in cell membrane potential is optically measured.