Functional & Molecular Study of Human Laryngeal Muscles

描述(申请人提供)：哺乳动物骨骼肌纤维可以 按重链(MyHC)和轻链(MyLC)的特性分类 它们所含的肌球蛋白(主要的马达蛋白)的异构体。有些是高度 人类眼外肌和合口肌中的特化肌纤维表达 无论是与特快或慢相关的新的MyHC亚型 收缩或未知泛函的异构体的异常组合 意义。初步证据表明，喉外肌 可表达眼外快速收缩的MyHC亚型和强直性MyHC 用于缓慢紧张性收缩的异构体。儿童对MyHC和MyLC基因表达的了解 人类喉部肌肉非常有限，并且有一种纤维型的分类方案 肌球蛋白含量与这些肌肉的收缩功能之间的关系是 缺乏。使用来自甲鳃(TA)两个腹部的肌肉样本 肌肉，声带内收肌和后部的两个腹部 本研究的首要目的是研究声带外展肌--环颧肌 是为这些肌肉开发一种纤维类型分类方案，基于 MyHC和MyLC鉴定采用组织化学和免疫组织化学方法。 第二个目标是确定空载缩短率(Vo)的最大速度 和皮肤纤维的比张力(Po)与MyHC表达和 第三个目标是将最大功率输出(Wmax)与激活联系起来 活体纤维的特性。最后，考虑到MyHC的异构性 MyHC基因在喉纤维中的表达及其与喉癌的关系 将评估异肌球蛋白含量，以确定共表达是稳定的还是 过渡状态。这项工作将提供详细的、关键的信息 关于MyHC在人类喉肌中的表达，表型 它们所包含的所有纤维类型的特征，以及关键的生理 每种纤维类型的属性。这一信息将识别生化和 喉部肌肉功能的生理标记物 结合临床观察，将提供有意义的 了解喉部肌肉的功能和发声功能障碍， 呼吸和吞咽。

DESCRIPTION (provided by applicant): Mammalian skeletal muscle fibers can be classified by characterization of the heavy chain (MyHC) and light chain (MyLC) isoforms of myosin (the primary motor protein) that they contain. Some highly specialized muscle fibers in human extraocular and jaw-closing muscles express either novel MyHC isoforms associated with especially rapid or slow contractions or unusual combinations of isoforms of unknown functional significance. Preliminary evidence suggests that extrinsic laryngeal muscles may express the extraocular MyHC isoform for rapid contraction and a tonic MyHC isoform for slow tonic contractions. Knowledge of MyHC and MyLC expression in human laryngeal muscle is very limited, and a fiber type classification scheme correlating myosin protein content to contractile function in these muscles is lacking. Using muscle samples from the two bellies of the thyroarytenoid (TA) muscle, a vocal cord adductor, and the two bellies of the posterior cricoarytenoid muscle (PCA), a vocal fold abductor, the first aim of this study is to develop a fiber type classification scheme for these muscles based on MyHC and MyLC identification as determined by histochemical and immunostaining. The second aim is to determine the maximum speed of unloaded shortening (Vo) and specific tension (Po) in skinned fibers relative to MyHC expression and the third aim is to relate maximum power output (Wmax) to activation characteristics in live fibers. Finally, given the heterogeneous nature of MyHC expression in laryngeal fibers, the relationship of MyHC gene expression to isomyosin content will be assessed to determine if coexpression is a stable or transitional condition. This work will provide detailed, pivotal information regarding MyHC expression in human laryngeal muscles, the phenotype characteristics of all the fiber types they contain, and key physiological properties of each fiber type. This information will identify biochemical and physiologic markers of laryngeal muscle function in a form which can be integrated with clinical observations, and which will provide significance understanding of laryngeal muscle function and dysfunction in voice, respiration and swallowing.