Voltage-Gated Sodium Channel Mutations can Exert Dominant-Negative Suppression by Coupled Gating

Introduction: Mutations in voltage-gated sodium channels have been linked to channelopathies such as cardiac arrhythmias, epilepsy and myotonia. We previously demonstrated that trafficking-deficient mutant channels could lead to a dominant-negative effect by impairing trafficking of the wild-type cardiac sodium channel (WT). We and others have also reported that sodium channel polymorphisms present on one construct can affect the gating of the WT on a separate construct suggesting gating cooperation between channels.