title: Insights into cardiac conduction system formation provided by HCN4 expression.
abstract: Specialized myocytes of the cardiac conduction system (CCS) are essential to coordinate sequential contraction of cardiac atria and ventricles. Anomalies of the CCS can result in lethal cardiac arrhythmias, including sick sinus syndrome and atrial or ventricular fibrillation. To develop future therapies and regenerative medicine aimed at cardiac arrhythmias, it is important to understand formation and function of distinct components of the CCS. Essential to this understanding is the development of CCS-specific markers. In this review, we briefly summarize available mouse models of CCS markers and focus on those involving the hyperpolarization cation-selective nucleotide-gated cation channel, HCN4, which selectively marks all components of the specialized CCS in adult heart. Recent studies have revealed, however, that HCN4 expression during development is highly dynamic in cardiac precursors. These studies have offered insights into the contributions of the first and second heart field to myocyte and conduction system lineages and suggested the timing of allocation of specific conduction system precursors during development. Altogether, they have highlighted the utility of HCN4 as a cell surface marker for distinct components of the CCS at distinct stages of development, which can be utilized to facilitate purification and characterization of CCS precursors in mouse and human model systems and pave the way for regenerative therapies.
authors.affiliation: Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Medicine, University of California, San Diego, San Diego, CA.
authors.forename: Xingqun
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Medicine, University of California, San Diego, San Diego, CA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA; Department of Pharmacology, University of California, San Diego, San Diego, CA. Electronic address: syevens@ucsd.edu.
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.affiliation: Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: yfsun@tongji.edu.cn.
authors.forename: Yunfu
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D019070:Cell Lineage; D006329:Heart Conduction System / Q000166:cytology / Q000502:physiology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D015221:Potassium Channels