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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Regulated and aberrant glycosylation modulate cardiac electrical signaling
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Regulated and aberrant glycosylation modulate cardiac electrical signaling

机译：调节和异常糖基化调节心脏电信号

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摘要

Millions afflicted with Chagas disease and other disorders of aberrant glycosylation suffer symptoms consistent with altered electrical signaling such as arrhythmias, decreased neuronal conduction velocity, and hyporeflexia. Cardiac, neuronal, and muscle electrical signaling is controlled and modulated by changes in voltage-gated ion channel activity that occur through physiological and pathological processes such as development epilepsy, and cardiomyopathy. Glycans attached to ion channels alter channel activity through isoform-specif ic mechanisms. Here we show that regulated and aberrant glycosylation modulate cardiac ion channel activity and electrical signaling through a cell-specific mechanism. Data show that nearly half of 239 glycosylation-associated genes (glycogenes) were significantly differentially expressed among neonatal and adult atrial and ventricular myocytes. The N-glycan structures produced among cardiomyocyte types were markedly variable. Thus, the cardiac glycome, defined as the complete set of glycan structures produced in the heart, is remodeled. One giycogene, ST8sia2, a polysialyltransferase, is expressed only in the neonatal atrium. Cardiomyocyte electrical signaling was compared in control and ST8sia2~((-/-)) neonatal atrial and ventricular myocytes. Action potential waveforms and gating of less sialylated voltage-gated Na~+ channels were altered consistently in ST8sia2~((-/-)) atrial myocytes. ST8sia2 expression had no effect on ventricular myocyte excitability. Thus, the regulated (between atrium and ventricle) and aberrant (knockout in the neonatal atrium) expression of a single giycogene was sufficient to modulate cardiomyocyte excitability. A mechanism is described by which cardiac function is controlled and modulated through physiological and pathological processes that involve regulated and aberrant giycosylation.
机译：患有Chagas病和其他异常糖基化疾病的数百万患者患有与电信号改变相一致的症状，如心律不齐，神经元传导速度降低和反射不足。心脏，神经元和肌肉的电信号传导受生理和病理过程（如发育性癫痫和心肌病）发生的电压门控离子通道活性变化的控制和调节。附着在离子通道上的聚糖通过同工型特异性机制改变通道活性。在这里，我们显示调节和异常糖基化通过细胞特异性机制调节心脏离子通道活性和电信号传导。数据显示，在239个糖基化相关基因（糖原）中，有近一半在新生儿和成年心房和心室肌细胞之间显着差异表达。在心肌细胞类型之间产生的N-聚糖结构明显不同。因此，被定义为心脏中产生的聚糖结构的完整集合的心脏糖原被重塑。一种新生基因，ST8sia2，一种聚唾液酸转移酶，仅在新生儿心房中表达。比较了对照组和ST8sia2〜（（-/-））新生儿心房和心室肌细胞的心肌电信号。在ST8sia2〜（（-/-））心房肌细胞中，唾液酸化的门控电压较低的Na〜+通道的动作电位波形和门控一直发生变化。 ST8sia2表达对心室肌细胞兴奋性没有影响。因此，单个糖原基因的调节表达（心房和心室之间）和异常表达（新生儿心房中的敲除）足以调节心肌细胞的兴奋性。描述了一种机制，通过该机制可通过涉及调节和异常糖基化的生理和病理过程来控制和调节心脏功能。

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  • 作者

    Marty L. Montpetit; Patrick J. Stocker; Tara A. Schwetz; Jean M. Harper; Sarah A. Norring; Lana Schaffer; Simon J. North; Jihye Jang-Lee; Timothy Gilmartin; Steven R. Head; Stuart M. Haslam; Anne Dell; Jamey D. Marth; Eric S. Bennett;

  • 作者单位

    Department of Molecular Pharmacology & Physiology, Programs in Cardiovascular Sciences and Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612;

    Department of Molecular Pharmacology & Physiology, Programs in Cardiovascular Sciences and Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612;

    Department of Molecular Pharmacology & Physiology, Programs in Cardiovascular Sciences and Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612;

    Department of Molecular Pharmacology & Physiology, Programs in Cardiovascular Sciences and Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612;

    Department of Molecular Pharmacology & Physiology, Programs in Cardiovascular Sciences and Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612;

    DNA Microarray Core, The Scripps Research Institute, La Jolla, CA 92037;

    Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, United Kingdom;

    Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, United Kingdom;

    DNA Microarray Core, The Scripps Research Institute, La Jolla, CA 92037;

    DNA Microarray Core, The Scripps Research Institute, La Jolla, CA 92037;

    Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, United Kingdom;

    Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, United Kingdom;

    Department of Cellular and Molecular Medicine, The Howard Hughes Medical Institute, University of California at San Diego, La Jolla, CA 92093;

    Department of Molecular Pharmacology & Physiology, Programs in Cardiovascular Sciences and Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    action potentials; cardiomyocyte; glycomics; ion channels; sialic acids;

    机译：动作电位;心肌细胞糖组学离子通道唾液酸;

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