Cardiac ion channel trafficking defects and drugs

Abstract

Fine control over the functional expression of cardiac ion channels is required to maintain normal action potential (AP) duration and QTc times. A growing number of drugs interfere with normal trafficking of ion channels to and from the plasma membrane, thereby altering the number of channels on the cell surface. Most drugs do this at clinically relevant concentrations, which may lead to potentially life-threatening cardiac arrhythmias. Recently, major progress has been made in the understanding of the subcellular mechanisms by which drugs affect the trafficking of ion channels, which is of great benefit for the development of ways to counteract these adverse drug effects. Pharmacological correction seems to be a promising approach to address the trafficking defects induced by several drugs. However, as pharmacological correction is hampered by concomitant direct channel block or unspecific effects, further studies are needed to improve its potential as a clinical therapy.