Introduction: KCNEs are beta-subunits of voltage-gated potassium channels (Kv), which are essential for repolarization of cardiomyocytes. The co-assembling of KCNEs with Kv alpha- subunits characterizes their functional properties. Mutations in the KCNE3 gene are associated with Brugada syndrome and atrial fibrillation (AF).
Methods: In this study we used a conventional generated Kcne3 knockout (KO) to investigate the role of KCNE3 in adult mouse heart. In vivo electrophysiology studies revealed a shortening of effective refractory period (ERP) in atria accompanied by AF in pacing induced.
Results: Furthermore, whole-cell patch clamp recordings of cardiomyocytes results in a higher current density in Kcne3 deficient atria, but ventricular myocytes were unaffected. Detailed functional analysis of atrial cardiomyocytes demonstrated an altered Kv channel properties of Kv4.3 (Ito) and Kv1.5 (Ikslow1) that might involve KChIP2, an interaction partner protein shared between Kv4.3 and Kv1.5.
Conclusions: Our novel mechanistic insights into the interaction of KCNE3 and these alpha subunits of Kv channels could help explain the selective effect of Kcne3 deficiency for atrial excitation, especially for development of AF