Effect of 23-day muscle disuse on sarcoplasmic reticulum Ca²⁺ properties and contractility in human type I and type II skeletal muscle fibers

Abstract

Lamboley CR, Wyckelsma VL, Perry BD, McKenna MJ, Lamb GD. Effect of 23-day muscle disuse on sarcoplasmic reticulum Ca 2ϩ properties and contractility in human type I and type II skeletal muscle fibers. J Appl Physiol 121: 483-492, 2016. First published June 30, 2016 doi:10.1152/japplphysiol.00337.2016.-Inactivity negatively impacts on skeletal muscle function mainly through muscle atrophy. However, recent evidence suggests that the quality of individual muscle fibers is also altered. This study examined the effects of 23 days of unilateral lower limb suspension (ULLS) on specific force and sarcoplasmic reticulum (SR) Ca 2ϩ content in individual skinned muscle fibers. Muscle biopsies of the vastus lateralis were taken from six young healthy adults prior to and following ULLS. After disuse, the endogenous SR Ca 2ϩ content was ϳ8% lower in type I fibers and maximal SR Ca 2ϩ capacity was lower in both type I and type II fibers (Ϫ11 and Ϫ5%, respectively). The specific force, measured in single skinned fibers from three subjects, decreased significantly after ULLS in type II fibers (Ϫ23%) but not in type I fibers (Ϫ9%). Western blot analyses showed no significant change in the amounts of myosin heavy chain (MHC) I and MHC IIa following the disuse, whereas the amounts of sarco(endo)plasmic reticulum Ca 2ϩ -ATPase 1 (SERCA1) and calsequestrin increased by ϳ120 and ϳ20%, respectively, and the amount of troponin I decreased by ϳ21%. These findings suggest that the decline in force and power occurring with muscle disuse is likely to be exacerbated in part by reductions in maximum specific force in type II fibers, and in the amount of releasable SR Ca 2ϩ in both fiber types, the latter not being attributable to a reduced calsequestrin level. Furthermore, the ϳ3-wk disuse in human elicits change in SR properties, in particular a more than twofold upregulation in SERCA1 density, before any fiber-type shift. IT IS WELL KNOWN that chronic muscle disuse in young healthy adults, as induced by spaceflight, bedrest, or immobilization, adversely affects muscle function. Although the loss of skeletal muscle mass induced by the disuse is widely acknowledged to contribute to this impairment, it has become increasingly evident that contractile dysfunction is disproportionately greater than decrements in cross-sectional area (CSA), as indicated by a decrease of specific force, suggesting a significant role played by decreased muscle "quality" in the dysfunction (4,9,15,33,51). It has been recently reported that the reduction of muscle quality can be attributed to a complex interaction of many factors that can affect neuromuscular transmission (4,24,42), muscle architecture (8, 9), muscle fiber phenotype (14,38), and contractile apparatus properties (20,21).Studies examining human muscle biopsies following a longterm period of muscle disuse have reported an overall shift in myosin heavy chain (MHC) isoforms from I to IIa to IIx (51), though this is not seen with shorter term disuse (6, 30). Interestingly, measures of contractile functio...

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Investigating human skeletal muscle physiology with unilateral exercise models: when one limb is more powerful than two

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