A sensitive mechanism for cation modulation of potassium current

The human ether a go-go-related gene (HERG) encodes ion channels that produce IKr (ref. 2), a potassium current that drives repolarization in many excitable cells. When the concentration of extracellular potassium ions ([K+]o) is raised, outward K+ current through HERG channels is paradoxically increased, despite a reduced electrochemical gradient, but the molecular mechanism is not fully understood. Here we show that extracellular sodium ions potently blocked HERG current in K+o-free conditions, and that low [K+]o (<5 mM) in the physiological range opposed block by sodium; hence the fine tuning that extracellular K+ confers on IKr actually represents modulation of sodium block by potassium.

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