Characterization of a Chinese KCNQ1 mutation (R259H) that shortens repolarization and causes short QT syndrome 2

Journal of Geriatric Cardiology : JGC
Zhi-Juan WuYang Li

Abstract

To evaluate the association between a KCNQ1 mutation, R259H, and short QT syndrome (SQTS) and to explore the electrophysiological mechanisms underlying their association. We performed genetic screening of SQTS genes in 25 probands and their family members (63 patients). We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that encode ion channels which contribute to the repolarization of the ventricular action potential, including KCNQ1, KCNH2, KCNE1, KCNE2, KCNJ2, CACNA1c, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. R259H-KCNQ1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type (WT) after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation (P > 0.05), whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H...Continue Reading

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transfection

Software Mentioned

Origin
pCLAMP

Related Concepts

Related Feeds

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Related Papers

Journal of Molecular and Cellular Cardiology
Yaxun SunGan-Xin Yan
Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society
A El HarchiJ C Hancox
Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Ulrike HenrionGuiscard Seebohm
© 2021 Meta ULC. All rights reserved