Abstract 13049: Electrophysiological Mechanism of Potassium Channel KCNQ1 p.V162M Mutation Induced Atrial Tachycardia and Epilepsy

Abstract

Objective: Arrhythmia and epilepsy are the causes of syncope and sudden death. Both of them are associated with abnormal function of potassium ion channels. Delayed rectified potassium current (IKs) is generated by combining the α subunit of potassium ion channel encoded by KCNQ1 gene with the β subunit encoded by KCNE1 gene. It plays an important role in electrical excitation and K+ circulation of nerve cells. In this study, a patient with atrial arrhythmia and epilepsy with a history of syncope was identified by genetic testing as having a mutation in the KCNQ1 p.V162M gene. The purpose of this study was to investigate the effect of KCNQ1 p.V162M mutation on the structure and function of potassium ion channels. Methods: The mutant plasmid KCNQ1-p.V162M was constructed for cell transfection. The expression of protein and mRNA were analyzed by western blotting and real-time quantitative PCR. The IKs of the two groups were detected by whole-cell patch clamp technique. Results: Whole exon gene sequencing revealed that the patient carried the KCNQ1 p.V162M mutation. The results of molecular biology experiment showed that mRNA, KCNQ1 total protein and membrane protein expressions in mutant group were significantly lower than those in wild group. Whole-cell patch clamp results showed that the peak current density and tail current of IKs in the mutant group were significantly decreased compared with those in the wild group, indicating that the mutation of KCNQ1 p.V162M could lead to decreased function of potassium ion channels. Conclusions: KCNQ1 p.V162M mutation can lead to decreased expression of KCNQ1 protein and decreased function of potassium ion channel, which may be the potential mechanism of atrial tachycardia and epilepsy induced by this mutation.