In patients as well as in mouse models, enteroviral infections, especially Coxsackie group B viruses (CVB1-6), frequently induce ventricular arrhythmias and sudden cardiac death. The cardiac action potential requires proper function of cardiac ion channels. CVB3 alters Kv7.1 channel trafficking potentially leading to changes in action potentials and increasing likelihood of arrhythmias. Genetic variants of cardiac ion channels can cause changes in channel trafficking that may preserve from CVB3 modulations and present an evolutionary advantage. Here, we show that a common polymorphic Kv7.1 channel variant uses alternative trafficking pathways and may thus exert a benefit during CVB3 infections. Genetic and pharmacological disruption of a CVB3-stimulated Serum- and Glucocorticoid inducible Kinase 1 (SGK1) pathways blunts Kv7.1 channel dysfunctions.
Our results suggest that escape from CVB3-induced SGK1-stimulation by genetic variation in Kv7.1 may be protective and inhibition of SGK1 may present a pharmacological approach to reduce the pro-arrhythmic risk associated with acute coxsackievirus infections.