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Life Sci. 2014 Mar 3;97(2):107-15. doi: 10.1016/j.lfs.2013.12.006. Epub 2013 Dec 15.

Cardiac expression and atrial fibrillation-associated remodeling of K₂p2.1 (TREK-1) K⁺ channels in a porcine model.

Author information

1
Department of Cardiology, Medical University Hospital, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
2
Institute of Nanotechnology, Karlsruhe Institute of Technology, P.O. Box 3640, D-76021 Karlsruhe, Germany.
3
Department of Cardiology, Medical University Hospital, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. Electronic address: dierk.thomas@med.uni-heidelberg.de.

Abstract

AIMS:

Effective management of atrial fibrillation (AF) often remains an unmet need. Cardiac two-pore-domain K(+) (K2P) channels are implicated in action potential regulation, and their inhibition has been proposed as a novel antiarrhythmic strategy. K2P2.1 (TREK-1) channels are expressed in the human heart. This study was designed to identify and functionally express porcine K2P2.1 channels. In addition, we sought to analyze cardiac expression and AF-associated K2P2.1 remodeling in a clinically relevant porcine AF model.

MAIN METHODS:

Three pK2P2.1 isoforms were identified and amplified. Currents were recorded using voltage clamp electrophysiology in the Xenopus oocyte expression system. K2P2.1 remodeling was studied by quantitative real time PCR and Western blot in domestic pigs during AF induced by atrial burst pacing.

KEY FINDINGS:

Human and porcine K2P2.1 proteins share 99% identity. Residues involved in phosphorylation or glycosylation are conserved. Porcine K2P2.1 channels carried outwardly rectifying K(+) currents similar to their human counterparts. In pigs, K2P2.1 was expressed ubiquitously in the heart with predominance in the atrial tissue. AF was associated with time-dependent reduction of K2P2.1 protein in the RA by 70% (7 days of AF) and 80% (21 days of AF) compared to control animals in sinus rhythm. K2P2.1 expression in the left atrium, AV node, and ventricles was not affected by AF.

SIGNIFICANCE:

Similarities between porcine and human K2P2.1 channels indicate that the pig may represent a valid model for mechanistic and preclinical studies. AF-related atrial K2P2.1 remodeling has potential implications for arrhythmia maintenance and antiarrhythmic therapy.

KEYWORDS:

Atrial fibrillation; Background potassium current; Cardiac action potential; Electrical remodeling; K(2P) channel; Membrane potential

PMID:
24345461
DOI:
10.1016/j.lfs.2013.12.006
[Indexed for MEDLINE]
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