The Popeye domain containing genes: essential elements in heart rate control.
| Title: | The Popeye domain containing genes: essential elements in heart rate control. |
|---|---|
| Authors: | Schindler RF; Heart Science Centre, Imperial College London, Harefield, United Kingdom.; Poon KL; Simrick S; Brand T |
| Source: | Cardiovascular diagnosis and therapy [Cardiovasc Diagn Ther] 2012 Dec; Vol. 2 (4), pp. 308-19. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: AME Publishing Company Country of Publication: China NLM ID: 101601613 Publication Model: Print Cited Medium: Print ISSN: 2223-3652 (Print) Linking ISSN: 22233652 NLM ISO Abbreviation: Cardiovasc Diagn Ther Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Publication: SHEUNG WAN, Hong Kong : AME Publishing Company; Original Publication: Hangzhou, China : CDT Office, [2011]- |
| 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. |
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| Grant Information: | MR/J010383/1 United Kingdom MRC_ Medical Research Council |
| Contributed Indexing: | Keywords: Sick sinus syndrome; cyclic AMP; genetically modified; membrane proteins; organisms; sinoatrial node; sinus arrest |
| Entry Date(s): | Date Created: 20131128 Date Completed: 20131127 Latest Revision: 20250529 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC3839166 |
| DOI: | 10.3978/j.issn.2223-3652.2012.12.01 |
| PMID: | 24282731 |
| Database: | MEDLINE |
Journal Article; Review