Abstract
Statins are among the most commonly prescribed drug classes, and their use is expected to increase due to recent changes in therapy guidelines. Although statins have been suggested to shorten QT interval in heart failure patients, the effect of this drug class on cardiac electrophysiology has been incompletely studied. Here we study the effect of statins on one of the major repolarizing currents in the heart, IKs. We show that in response to a known stress stimulus (sustained alpha-AR stimulation), IKs undergoes clathrin-dependent internalization. Statin treatment inhibits this internalization. Our results suggest that statin regulates IKs internalization by inhibiting activation of Rab5, a GTPase involved in endocytic pathway regulation. We observe no significant effect of statin treatment on unstimulated IKs function and acute receptor regulation. Our results suggest that statins may prevent pathological QT prolongation in heart failure patients by inhibiting pathological remodeling and IKs internalization, while maintaining physiological trafficking and function of the channel.
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