Dataset Information

?(IV)-Spectrin regulates TREK-1 membrane targeting in the heart.

ABSTRACT:

Aims

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.

Methods and results

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 ?(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 ?(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 ?(IV)-spectrin levels in human heart failure.

Conclusions

These data provide new insight into membrane targeting of TREK-1 in the heart and establish a broader role for ?(IV)-spectrin in organizing functional membrane domains critical for normal heart function.

SUBMITTER: Hund TJ

PROVIDER: S-EPMC3958619 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Hund Thomas J TJ Snyder Jedidiah S JS Wu Xiangqiong X Glynn Patric P Koval Olha M OM Onal Birce B Leymaster Nicholas D ND Unudurthi Sathya D SD Curran Jerry J Camardo Celia C Wright Patrick J PJ Binkley Philip F PF Anderson Mark E ME Mohler Peter J PJ

Cardiovascular research 20140120 1

<h4>Aims</h4>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.<h4>Methods and results</h4>Here, we report a novel molecular pathway for membrane targe ...[more]

PMID: 24445605

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