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Variable function and expression of drug transporters have been proposed as mechanisms contributing to variable response to drug therapy. Block of the HERG channel, encoding IKr, can lead to serious arrhythmias, and a key drug-blocking site in HERG has been identified on the intracellular face of the pore. We begin to advance the hypothesis that active drug uptake enhances IKr block.

The Organic Cation Transporter, OCTN1, Expressed in the Human Heart, Potentiates Antagonism of the HERG Potassium Channel