The Popeye domain containing genes: essential elements in heart rate control

http://www.thecdt.org/article/view/1289

 

Author Roland F. Schindler, Kar Lai Poon, Subreena Simrick, Thomas Brand

Abstract

The Popeye domain containing (Popdc) gene family displays preferential expression in skeletal muscle and heart. Only recently a significant gain in the understanding of the function of Popdc genes in the heart has been obtained. The Popdc genes encode membrane proteins harboring an evolutionary conserved Popeye domain, which functions as a binding domain for cyclic adenosine monophosphate (cAMP). Popdc proteins interact with the two-pore channel TREK-1 and enhance its current. This protein interaction is modulated by cAMP. Null mutations of members of the Popdc gene family in zebrafish and mouse are associated with severe cardiac arrhythmia phenotypes. While in zebrafish an atrioventricular block was prevalent, in mouse a stress-induced sinus bradycardia was observed, which was due to the presence of sinus pauses. Moreover, the phenotype develops in an age-dependent manner, being absent in the young animal and becoming increasingly severe, as the animals grow older. This phenotype is reminiscent of the sick sinus syndrome (SSS), which affects mostly the elderly and is characterized by the poor ability of the cardiac pacemaker to adapt the heart rate to the physiological demand. While being a prevalent disease, which is responsible for a large fraction of pacemaker implantations in Western countries, SSS is poorly understood at the molecular level. It is therefore expected that the study of the molecular basis of the stress-induced bradycardia in Popdc mice will shed new light on the etiology of pacemaker disease.

2 responses to “The Popeye domain containing genes: essential elements in heart rate control

  1. In this review article, the authors discuss the molecular basis of the stress-induced bradycardia and specifically the Popeye domain containing (Popdc) gene family.

  2. The author Professor Thomas Brand, Chair in Developmental Dynamics at the Heart Science Centre at the Imperial College in London and his colleagues explain that the Popeye domain containing (Popdc) gene family has so far received only limited attention by the scientific community.
    In this review the potential role of the Popdc genes is outlined. They encode plasma membrane-localized cAMP-binding proteins involved in myocardial stress signalling and null mutants in mice have a bradyarrhythmia, which develops in an age-dependent manner.

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