Myosin Heavy Chain Isoforms in Mammalian Intrinsic Laryngeal Muscles: A Systematic Review

Objectives: This systematic review surveys all available literature on the myosin heavy chain (MHC) isoforms expressed in the intrinsic laryngeal skeletal muscles of mammalian species, including humans. As key determinants of a muscle fiber’s contractile properties, MHC isoforms can reveal valuable information about a muscle’s fatigability, responsiveness to denervation, aging, or pathology, and potential for training adaptations. Clinicians and researchers alike may benefit from such information as they attempt to formulate targeted exercise therapies or draw inferences about laryngeal muscle from the limb skeletal muscle literature.

Methods: We searched the Embase, Scopus, Medline, Web of Science, and Cochrane databases for studies that quantified the muscle fiber or MHC complements of mammalian intrinsic laryngeal muscles, regardless of the techniques used to make such measurements (e.g., myofibrillar ATPase staining, immunohistochemistry, SDS-PAGE/Western blotting, etc.). Following PRISMA guidelines for systematic reviews, 1525 non-duplicate papers were identified, of which 372 were selected for full-text screening. 109 papers were included in the final analysis.

Results: MHC isoform expression within the intrinsic laryngeal muscles varies markedly by age, species, and health/disease status. Irrespective of these factors, unusual MHC isoforms are expressed in the intrinsic larynx, including embryonic, neonatal, extraocular, and (per some authors) laryngeal MHCs. Hybrid muscle fibers, single-fiber MHC isoform asymmetries, and molecular markers of muscle remodeling in the absence of injury further complicate our understanding of the contractile properties of these muscles.

Discussion: Intrinsic laryngeal muscle fibers are strikingly heterogeneous from species to species, from person to person, and even from fiber to fiber. Although voice scientists may be tempted to frame intrinsic laryngeal muscles and limb skeletal muscles as analogous, extant data suggest that the intrinsic muscles of the larynx have unique physiological adaptations, possibly secondary to their evolutionary role in airway protection and management. The fields of genomics, proteomics, and medical imaging will continue to define the physiological niches that these muscles occupy. It falls to clinical scientists to translate physiology into function.