Symposia

AimThe voltage-gated potassium (Kv) ion channel Kv7.1/KCNE1 plays an important role in tuning cardiac excitability.Loss of function of Kv7.1/KCNE1 is linked to conditions like Long QT Syndrome.Therefore, understanding how Kv7.1/KCNE1 is modulated by endogenous and exogenous compounds is of broad interest in the context of cardiac arrhythmias.In this overall project, we aim to understand how the Kv7.1/KCNE1 channel is modulated by endogenous and synthetic steroid hormones, such as estrogens. Methods & ResultsWe use electrophysiology techniques in combination with molecular dynamics simulations and synthetic chemistry to characterize effects and determine the underlying molecular mechanisms.From these combined approaches, we propose a steroid hormone binding site in Kv7.1/KCNE1 underlying channel inhibition by specific estrogens. ConclusionsWe envision that the molecular understanding of how ligands like steroid hormones modulate the Kv7.1/KCNE1 channel will open new avenues for future risk assessment and potentially guide safe drug development.