Myosin heavy chains in extraocular muscle fibres: Distribution, regulation and function

Abstract

This review examines kinetic properties and distribution of the 11 isoforms of myosin heavy chain (MyHC) expressed in extraocular muscle (EOM) fibre types and the regulation and function of these MyHCs. Although recruitment and discharge characteristics of ocular motoneurons during fixation and eye movements are well documented, work directly linking these properties with motor unit contractile speed and MyHC composition is lacking. Recruitment of motor units according to Henneman's size principle has some support in EOMs but needs consolidation. Both neurogenic and myogenic mechanisms regulate MyHC expression as in other muscle allotypes. Developmentally, multiply‐innervated (MIFs) and singly‐innervated fibres (SIFs) are derived presumably from distinct myoblast lineages, ending up expressing MyHCs in the slow and fast ends of the kinetic spectrum respectively. They modulate the synaptic inputs of their motoneurons through different retrogradely transported neurotrophins, thereby specifying their tonic and phasic impulse patterns. Immunohistochemical analyses of EOMs regenerating in situ and in limb muscle beds suggest that the very impulse patterns driving various ocular movements equip effectors with appropriate MyHC compositions and speeds to accomplish their tasks. These experiments also suggest that satellite cells of SIFs and MIFs are distinct lineages expressing different MyHCs during regeneration. MyHC compositions and functional characteristics of orbital fibres show longitudinal variations that facilitate linear ocular rotation during saccades. Palisade endings on global MIFs are postulated to respond to active and passive tensions by triggering axon reflexes that play important roles during fixation, saccades and vergence. How EOMs implement Listings law during ocular rotation is discussed.

Transmitter and ion channel profiles of neurons in the primate abducens and trochlear nuclei

“…Earlier work on extraocular muscles suggested the possibility that slow eye movements and gaze holding is achieved by slow-tonic (non-twitch) non-fatigable fibers, while fast eye movements such as saccades are produced by fast-twitch fatigable fibers, as observed in vertebrate skeletal muscles (Bormioli et al 1980;Close and Hoh 1968;Henneman et al 1965;Hoh 2020;Ugolini et al 2006). However, the expression of numerous myosin heavy chain isoforms that define contraction characteristics in extraocular muscles suggests that the wide range of eye movements might be differentially controlled through the recruitment of several fiber types, rather than the often-emphasized bimodal distribution (Hoh 2020;Horn and Straka 2021).…”

“…Earlier work on extraocular muscles suggested the possibility that slow eye movements and gaze holding is achieved by slow-tonic (non-twitch) non-fatigable fibers, while fast eye movements such as saccades are produced by fast-twitch fatigable fibers, as observed in vertebrate skeletal muscles (Bormioli et al 1980;Close and Hoh 1968;Henneman et al 1965;Hoh 2020;Ugolini et al 2006). However, the expression of numerous myosin heavy chain isoforms that define contraction characteristics in extraocular muscles suggests that the wide range of eye movements might be differentially controlled through the recruitment of several fiber types, rather than the often-emphasized bimodal distribution (Hoh 2020;Horn and Straka 2021). Indeed, apart from a classification according to the arrangement into an orbital and a global layer, extraocular muscle fibers can be subdivided into up to six types according to structural and histochemical properties such as fiber diameter, sarcoplasmic reticulum development, number of mitochondria and oxidative enzyme content (Shall and Goldberg 1992;Spencer and Porter 2006).…”

“…Indeed, apart from a classification according to the arrangement into an orbital and a global layer, extraocular muscle fibers can be subdivided into up to six types according to structural and histochemical properties such as fiber diameter, sarcoplasmic reticulum development, number of mitochondria and oxidative enzyme content (Shall and Goldberg 1992;Spencer and Porter 2006). In these analyses, global and orbital SIFs, as well as orbital MIFs, are arranged along a spectrum of fast/slow and fatigable/fatigue-resistant properties, whereas global MIFs are positioned at the non-twitch/slow-tonic end containing the slowest myosin heavy chain isoforms (Close and Hoh 1968;Hernández et al 2019;Hoh 2020;Matyushkin 1964).…”

Mass Spectrometric Profiling of Extraocular Muscle and Proteomic Adaptations in the mdx-4cv Model of Duchenne Muscular Dystrophy

“…Characteristic biological features of EOMs include (i) unique developmental processes with specific upstream activators [ 7 , 8 ], (ii) longitudinal dispersion of multiterminal neuromuscular junctions [ 9 , 10 , 11 ], (iii) morphologically distinct muscle spindles as compared to conventional somatic spindles [ 12 ], (iv) an unusually high capacity for cellular remodelling and fibre regeneration [ 13 , 14 ], (v) an efficient calcium handling and extrusion system [ 15 ], (vi) high levels of fatigue resistance even in extremely fast-twitching fibres [ 16 ] and (vii) distinguishing combinations of contractile protein isoform expression patterns [ 17 ]. Another striking biomedical feature of EOMs is their apparent resistance to degeneration in X-linked muscular dystrophy [ 18 , 19 , 20 ].…”

Pregnancy

“…Recent results regarding developmental myogenesis 24 and its regulators 25 shed light on physiological and potentially aberrant muscle development, with potential therapeutic implications.…”