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hERG potassium channels and cardiac arrhythmia

Abstract

hERG potassium channels are essential for normal electrical activity in the heart. Inherited mutations in the HERG gene cause long QT syndrome, a disorder that predisposes individuals to life-threatening arrhythmias. Arrhythmia can also be induced by a blockage of hERG channels by a surprisingly diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials. Insights gained from the crystal structures of other potassium channels have helped our understanding of the block of hERG channels and the mechanisms of gating.

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Figure 1: Multiple ion channel currents shape the cardiac action potential.
Figure 2: Conformation of a single hERG channel is voltage dependent.
Figure 3: Reduced hERG current delays ventricular repolarization and can induce arrhythmia.
Figure 4: Structural features of voltage-gated K+ channels.
Figure 5: Model of the hERG drug-binding site.

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Sanguinetti, M., Tristani-Firouzi, M. hERG potassium channels and cardiac arrhythmia. Nature 440, 463–469 (2006). https://doi.org/10.1038/nature04710

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