Supertrafficking ion channel found to be arrhythmia culprit

Supertrafficking ion channel found to be arrhythmia culprit
Single-cell trafficking properties are analyzed for WT versus R231C KCNQ1 in HEK293 cells. Credit: Journal of Biological Chemistry (2021). DOI: 10.1016/j.jbc.2021.100423

The potassium channel KCNQ1 plays a critical role in the cardiac action potential—the electrical activity underlying heart muscle contraction. Inherited mutations resulting in loss of channel function or gain of function (GOF) cause heart rhythm abnormalities.

Charles Sanders, Ph.D., and colleagues surveyed known disease-linked GOF mutations in KCNQ1 and found that seven of 15 increased the amount of KCNQ1 that reached the , an effect called "supertrafficking."

The researchers further characterized a particular supertrafficking mutant channel, R231C, which had plasma membrane levels five times the wild-type channel. Whole-cell electrophysiology showed that the R231C channel is incorrectly always open, but that its open-state current is only 20% that of the wild-type channel. The GOF of R231C reflects the combined effects of supertrafficking, constitutive channel activation, and reduced ion flux.

These findings, reported in the Journal of Biological Chemistry, establish that membrane protein supertrafficking can contribute to .


Explore further

Long QT syndrome—revealed

More information: Hui Huang et al. Disease-linked supertrafficking of a potassium channel, Journal of Biological Chemistry (2021). DOI: 10.1016/j.jbc.2021.100423
Journal information: Journal of Biological Chemistry

Citation: Supertrafficking ion channel found to be arrhythmia culprit (2021, April 16) retrieved 7 May 2021 from https://medicalxpress.com/news/2021-04-supertrafficking-ion-channel-arrhythmia-culprit.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
6 shares

Feedback to editors

User comments