A novel mechanism for LQT3 with 2:1 block: A pore-lining mutation in Nav1.5 significantly affects voltage-dependence of activation

Our data suggest a novel mechanism for LQT3, a result of a hyperpolarizing shift in the steady state activation relationship and re-activation of Nav1.5 towards a higher open probability during repolarization of the cardiac action potential. This results in an increased number of open-activated sodium channels, and so drugs that bind this state preferentially are expected to shorten the QTc more than those that favour the inactivated state.