Age-Associated Ion Channel Localization and Expression Changes Regulate Cardiac Sodium Gain-of-Function

Abstract

Madison B. Nowak, Steven Poelzing, and Seth H. Weinberg Age-Associated Ion Channel Localization and Expression Changes Regulate Cardiac SodiumGain-of-Function Action potentials in the heart are initiated by sodium (Na+) ion influx via voltage-gated Na+channels. Na+ channel gain-of-function (GoF) mutations associated with the long QT type-3(LQT3) syndrome can produce a late Na+ current, triggering pro-arrhythmic early after-depolarizations (EADs) that prolong the action potential duration (APD). Recently, we showedthat preferential localization of Na+ channels at the intercalated disk and narrow intercellular cleftssuppress EADs and APD prolongation in LQT3-associated models (Nowak, et al., Biophysical J, 2020).