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Biological approaches to generating cardiac biopacemaker for bradycardia

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Author:: No author available

Journal Title:: ACTA PHYSIOLOGICA SINICA

Issue:: 5

DOI:: 10.3321/j.issn:0371-0874.2007.05.004

Key Word:: 窦房结;生物起搏点;基因;干细胞;超极化活化环核苷酸门控通道;sinoatrial node;biological pacemaker;gene;stem cell;hyperpolarization-activated cyclic-nucleotide-modulated channel

Abstract： Normal rhythm in a healthy human heart originates from the natural biological pacemaker, the sinoatrial (SA) node which locates in the right atrium. SA node dysfunction or atrial-ventricular (AV) conduction block causes improper heart rate (bradycardia).Such dysfunction, if severe enough, is currently treated by implanting an electronic pacemaker which has been well established technically, but there are some limitations and inadequacies. Recently, progress in developing engineered cardiac biopacemakers with use of genes or cells has been made in experimental animal models. The hyperpolarization-activated cyclic-nucleotide-modulated(HCN) channel (pacemaker channel) modulates cardiac automaticity via the hyperpolarization-activated cation current (If). HCN genes have been delivered to animal myocardium via viral vectors or HCN-transferred cells for recreating biological pacemakers. Approaches with non-HCN genes or transplantation of beating cells are also novel and have been investigated for generating cardiac biopacers. This article summarizes the progresses in research on recreation of cardiac biopacemakers. Genetically engineered biological pacemaker holds great promise to potentially cure severe bradycardia if critical issues, such as their stability and longevity, are properly solved.

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