Functional & Molecular Study of Human Laryngeal Muscles

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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.