Human muscle spindles : Complex morphology and structural organisation

Sammanfattning: lntroduction: Muscle spindIes are skeletal muscle mechanoreceptors that mediate the stretch reflex and provide axial and limb position information to the central nervous system. Theyhave been proposed to playamajor role in the pathophysiology of muscle pain. Knowledge about the normal human muscle spindIes is needed in order to understand their role in muscle disease or dysfunction.The aim of this study was to investigate the fiber content and MyHC composition of the muscle spindIes in the human biceps brachii (88) and deep muscles of the neck (DN); to determine whether there are age-related changes in human muscle spindIes with respect to structure and MyHC composition; to investigate the distribution of SERCA isoforms and to evaluate whether there is a coordinated expression of SERCA and MyHC isoforms in intrafusal fibers. The myosin heavy chain (MyHC) content correlates to contraction velocity and force and the sarcoplasmic reticulum Ca2+ ATPase (SERCA) is a major determinant ofmuscle fiber relaxation velocity .Methods: Muscle specimens obtained from young and old subjects were serially sectioned and the pattem of distribution of different proteins along the length of the intrafusal fibers was revealed by immunocytochemistry .The MyHC content of single muscle spindIes was assessed with SDS-PAGE and immunoblots.Results: There were clear differences between 88 and DN with regard to the morphology and MyHC composition of muscle spindIes. Virtually each muscle spindIe in th~ 88, but not in the DN, had a unique allotment of numbers of bagl, bag2 and chain fibers. In DN, a number of muscle spindIes lacked either bagl or bag2 fibers. Four major MyHC isoforms (MyHCI, Ila, a.- cardiac and intrafusal) were detected by SDS-PAGE. In both 88 and DN, immunocytochemistry revealed co-expression of several MyHC isoforms in each intrafusal fiber and regional heterogeneity. 8oth nuclear bagl and bag2 fibers contained slow tonic MyHC uniformly and MyHCI, a.-cardiac, embryonic and fetal with regional variations. Nuclear chain fibers contained MyHCIla, embryonic and fetal and in the 88 also MyHCIIx.The total number of intrafusal fibers per spindIe decreased significantly with aging, due to a significant reduction in the number of nuclear chain fibers. The patterns of MyHC expression were also affected by aging.The bagl fibers predominantly contained both SERCA isoforms in the encapsulated region. The bag2 fibers were more heterogeneous in their SERCA composition and 16-27% of them lacked both isoforms. Chain fibers contained SERCAI. There was a poor correlation between the MyHC and SERCA isoforms in nuclear bag fibers, whereas a strong correlation existed between MyHCIla and SERCAI in the nuclear chain fibers.Conclusions: Human muscle spindles, each being unique, proved to be more complex than anticipated. The clear differences shown between the 88 and DN muscle spindIes suggest functional specialization in the control of movement among different human muscles. Aging apparently had profound effects on intrafusal fiber content and MyHC composition. The age- related changes in muscle spindIe phenotype may reflect deterioration in sensory and motor innervation and are likely to have a detrimental impact on motor control in the elderly.