Functional & Molecular Study of Human Laryngeal Muscles

描述（由申请人提供）：哺乳动物骨骼肌纤维可 根据重链（MyHC）和轻链（MyLC）的特征分类 肌球蛋白（主要的运动蛋白）的同种型。一些高度 人类眼外肌和下颌闭合肌中的特化肌纤维表达 新的MyHC亚型与特别快速或缓慢的 收缩或未知功能的亚型的异常组合 意义初步证据表明喉外肌 可能表达眼外MyHC亚型，用于快速收缩和强直性MyHC 缓慢紧张性收缩的同种型。MyHC和MyLC表达的知识， 人类喉肌是非常有限的， 将肌球蛋白含量与这些肌肉的收缩功能相关联， 缺乏使用甲杓肌（TA）两个腹部的肌肉样本， 肌肉，声带内收肌，和两个腹部的后 环杓肌（PCA），声带外展肌，本研究的第一个目的 是为这些肌肉开发一种纤维类型分类方案， 通过组织化学和免疫染色确定MyHC和MyLC鉴定。 第二个目的是确定无负荷缩短的最大速度（Vo） 和比张力（Po）在皮肤纤维相对于MyHC表达和 第三个目的是将最大功率输出（Wmax）与激活相关联 活纤维的特征。最后，鉴于MyHC的异质性， MyHC基因在喉纤维中的表达，MyHC基因表达与 将评估异肌球蛋白含量以确定共表达是否是稳定的或 过渡状态这项工作将提供详细的关键信息 关于MyHC在人喉肌中的表达， 它们所包含的所有纤维类型的特性，以及关键的生理特性， 每种纤维的特性。这些信息将确定生物化学和 喉肌功能的生理标志物，其形式可以是 结合临床观察，这将提供意义 了解喉肌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.