Genetic mutations of voltage-gated ion channels associated with channelopathies

This paper explores how mutants of each type of voltage-gated ion channel associated with cardiac channelopathies differ from wildtype genes. 1 in 2000 people is estimated to have Long QT Syndrome (LQTS), a form of cardiac channelopathy that may lead to sudden cardiac death (SCD). Cardiac channelopathies are often caused by mutants that alter voltage-gated ion channels. The main voltage-gated ion channels are sodium, potassium, and calcium-gated ion channels. Structurally, they are composed of proteins that construct ion-conducting pores through the cellular membrane and units influencing their gating and other cellular interactions. Specifically, mutants may cause the formation of abnormal proteins, thus causing deformations in ion channel structure and malfunctioning in electrochemical functions such as supporting normal cardiac activity. Normal cardiac activity is based on action potential phases, with sodium, potassium, and calcium ion influxes and effluxes contributing to this function. Each phase is associated with corresponding intervals and waves, which are evident on an electrocardiogram and reflect a specific normal duration per phase. Structural alterations in ion channels may lead to abnormal repolarization/depolarization durations, which cause various syndromes and symptoms such as SCD or LQTS. Focusing specifically on LQTS, the most prevalent types (LQT1, LQT2, LQT3) result from KCNQ1, KCNH2, and SCN5A mutations, respectively. Each LQTS is caused by a different mutation, different specific ion channels, and varying triggers and symptoms, such as adrenergic stimuli, auditory stimuli, and death during sleep, which target LQT1, 2, and 3, respectively. In conclusion, mutants cause structural deformities that differ from wildtype genes, which lead to cardiac activity abnormalities.