Modification of KCNH2-encoded cardiac potassium channels by KCNE1 polymorphism.

fects. Co-expression of KCNE1 (D76N) or KCNE1 (D85N) increases the susceptibility to clarithromycin, a macrolide antibiotic, lowering the IC50 to 1/3–2/3, whereas that of KCNE1 (A8V) decreases the susceptibility, doubling the IC50.1 Coexpression of KCNE1 (A8V), KCNE1 (D76N), or KCNE1 (D85N) increases the susceptibility to cisapride, a gastric prokinetic drug, lowering the IC50 to 1/2.1 Co-expression of either of the mutants does not affect the susceptibility to quinidine, a class I antiarrhythmic drug.1 As compared with KCNE1 (38G), co-expression of KCNE1 (38S) increases the susceptibility to E-4031, an experimental class III antiarrhythmic drug, lowering the apparent dissociation constant to 1/4.2 The effects differ considerably, depending on the type of KCNE1 mutants/ variant and drug. In future studies, researchers and clinicians engaged in cardiac channelopathy should keep an eye out for the dual pathogenic actions of KCNE1 mutants via the IKr and IKs channels. In addition, the previously identified KCNE1 mutants, including ones that were judged to be ineffective on IKs channel function, await re-analysis in the light of their modulatory action on the IKr channel.