An In-Silico Study on Effect of KCNQI P535T Mutation in Cardiac Ventricular Cells

Abstract

Sudden death is mostly due to cardiac diseases such as arrhythmia. In general, arrhythmia is caused due to mutation in certain genes (inherited), damage to tissues or exposure to certain drugs (induced). P535T is a mutation whose clinical significance is not known yet. Therefore, this study aims to perform a simulation study on P535T mutation in the KCNQI gene of the potassium ion channel KV7.1 in the cardiac ventricular epicardial (epi) and mid myocardial (M) cell. This paper addresses the effect of P535T mutation on an epi and M cell for three conditions (wild type, heterozygous and homozygous) of cells. A comparison of slow delayed rectifier potassium current (IKs) has been conducted. The effect of P535T mutation on the action potential (AP) of the epi and M cell is also studied. Results show the existence of delayed repolarization in the ventricular epicardial and the M cells. This may lead to Long QT Syndrome (LQTS) which could result in life-threatening arrhythmias such as Torsade de Pointes (TdP), Jervell and Lange-Nielsen syndrome (JLNS) and Romano-Ward syndrome (RWS).