Effects of a persistent sodium current through mutated hnav1.5 sodium channels on intracellular ionic homeostasis in a ventricular cell model

Abstract

In LQT3 patients, SCN5A mutations were found that lead to a small fraction of persistent hNav1.5 current. We explored the effects of such a change on the intracellular ionic homeostasis in a model of guinea-pig cardiac ventricular cell. At steady-state under 1 Hz stimulation, the presence of a persistent Na⁺ current (I_Nap) with g _Nap 0.02 ms/cm² led to a prolongation of the action potential from 153 ms (control) to 223 ms and an increase of [Na ⁺]i, diastolic and systolic [Ca²⁺]_i and [Ca²⁺]_SRup by 10%, 30%, 40% and 43%, respectively. These changes were larger at 3 Hz. Such intracellular Na⁺ and Ca²⁺ overload was not found when the action potential prolongation (to 222 ms at 1 Hz) was due to decreased I_Kr and I_Ks currents. The model with I_Nap became arrhythmo genie when [K⁺]_e was lowered from 5.4 to 5.0 mM, whereas control and low K⁺ current models did not produce arrhythmias even when [K⁺]_e was 2.5 mM