Referenced in: none

Automatically associated channels: TREK1

Title: β(IV)-Spectrin regulates TREK-1 membrane targeting in the heart.

Authors: Thomas J Hund, Jedidiah S Snyder, Xiangqiong Wu, Patric Glynn, Olha M Koval, Birce Onal, Nicholas D Leymaster, Sathya D Unudurthi, Jerry Curran, Celia Camardo, Patrick J Wright, Philip F Binkley, Mark E Anderson, Peter J Mohler

Journal, date & volume: Cardiovasc. Res., 2014 Apr 1 , 102, 166-75

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24445605

Abstract
Cardiac function depends on the highly regulated and co-ordinate activity of a large ensemble of potassium channels that control myocyte repolarization. While voltage-gated K(+) channels have been well characterized in the heart, much less is known about regulation and/or targeting of two-pore K(+) channel (K(2P)) family members, despite their potential importance in modulation of heart function.Here, we report a novel molecular pathway for membrane targeting of TREK-1, a mechano-sensitive K(2P) channel regulated by environmental and physical factors including membrane stretch, pH, and polyunsaturated fatty acids (e.g. arachidonic acid). We demonstrate that β(IV)-spectrin, an actin-associated protein, is co-localized with TREK-1 at the myocyte intercalated disc, associates with TREK-1 in the heart, and is required for TREK-1 membrane targeting. Mice expressing β(IV)-spectrin lacking TREK-1 binding (qv(4J)) display aberrant TREK-1 membrane localization, decreased TREK-1 activity, delayed action potential repolarization, and arrhythmia without apparent defects in localization/function of other cardiac potassium channel subunits. Finally, we report abnormal β(IV)-spectrin levels in human heart failure.These data provide new insight into membrane targeting of TREK-1 in the heart and establish a broader role for β(IV)-spectrin in organizing functional membrane domains critical for normal heart function.