Exploring single nucleotide polymorphisms in the KCNQ1 gene associated with cardiac disorders

Abstract

Abstract Voltage gated potassium ion channels play a crucial role in the proper functioning of excitable cells, the appropriate secretion of hormones and neurotransmitters and especially in the maintenance of cardiac function. Among these channels, KCNQ1 channel has significant importance in modulating the action potential, in facilitating dynamic cellular repolarization of cardiac tissues and in regulating the water and salt balance in various tissues throughout the human body. The differential activity of KCNQ1 channels in these tissues is facilitated by accessory proteins and modulating factors that modify the properties of the KCNQ1 channel. KCNQ1 is different from other potassium ion channels as it has the ability to act as either a voltage-dependent channel that requires membrane depolarization for its activation or a fundamentally active channel. Mutations including indels and single nucleotide polymorphisms in the KCNQ1 gene result in dysfunction of the channel causing a number of different disorders and syndromes including short and long QT disorders, Jervell-Lange Nielsen Syndrome, Romano-Ward Syndrome and familial atrial fibrillation. This article reviews the unique structural and functional properties, the diverse physiological roles of KCNQ1 channel with a major focus on the mutational spectrum of the KCNQ1 gene, its implications and the therapeutic approaches being employed to manage the resultant disorders.