Effect of long-term muscle paralysis on human single fiber mechanics

Abstract

This study compared human muscles following long-term reduced neuromuscular activity to those with normal functioning regarding single fiber properties. Biopsies were obtained from the vastus lateralis of 5 individuals with chronic (Ͼ3 yr) spinal cord injury (SCI) and 10 able-bodied controls (CTRL). Chemically skinned fibers were tested for active and passive mechanical characteristics and subsequently classified according to myosin heavy chain (MHC) content. SCI individuals had smaller proportions of type I (11 Ϯ 7 vs. 34 Ϯ 5%) and IIa fibers (11 Ϯ 6 vs. 31 Ϯ 5%), whereas type IIx fibers were more frequent (40 Ϯ 13 vs. 7 Ϯ 3%) compared with CTRL subjects (P Ͻ 0.05). Cross-sectional area and peak force were similar in both groups for all fiber types. Unloaded shortening velocity of fibers from paralyzed muscles was higher in type IIa, IIa/IIx, and IIx fibers (26, 65, and 47%, respectively; P Ͻ 0.01). Consequently, absolute peak power was greater in type IIa (46%; P Ͻ 0.05) and IIa/IIx fibers (118%; P Ͻ 0.01) of the SCI group, whereas normalized peak power was higher in type IIa/IIx fibers (71%; P Ͻ 0.001). Ca 2ϩ sensitivity and passive fiber characteristics were not different between the two groups in any fiber type. Composite values (average value across all fibers analyzed within each study participant) showed similar results for cross-sectional area and peak force, whereas maximal contraction velocity and fiber power were more than 100% greater in SCI individuals. These data illustrate that contractile performance is preserved or even higher in the remaining fibers of human muscles following reduced neuromuscular activity. chemically skinned fibers; unloaded shortening velocity; fiber power; passive tension; spinal cord injury MUSCLE UNLOADING OCCURS in a variety of conditions, such as immobilization, disease, paralysis, or exposure to microgravity. The absence of normal weight-bearing activity induces a rapid decrease in muscle mass and strength, especially of antigravity muscles (1, 25). Muscle atrophy induced by unloading is associated with several structural changes, such as modifications of the myosin heavy chain (MHC) isoform expression, inducing fiber-type transitions toward a higher proportion of fast type II fibers. Experiments based on single fiber models have demonstrated great sensitivity in detecting also a certain degree of functional variability of fibers expressing the same MHC isoforms, especially when the pattern of muscle activity changes. Human studies involving 17 days of bed rest (27, 28) or spaceflight (26) revealed that maximal single fiber force (P 0 ) from the soleus muscle was decreased, mainly as a result of a decline in fiber cross-sectional area (CSA), and that maximal unloaded shortening velocity (V 0 ) was increased. Consequently, single fiber power was either maintained or depressed, depending on the study participant or fiber type (29), with fibers expressing type I MHC being generally more affected. Muscle unloading up to 4 mo in a long-term bed-rest study induced a similar ...

Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles

“…However, studies on human muscle paralysis, induced by spinal cord injury (SCI), found that MyHC isoform composition can shift from slow to fast (Malisoux et al, 2007;Biering-Sørensen et al, 2009). The results conflict with our study and many others on muscle denervation induced by BoNT/A.…”

Slow myosin heavy chain expression in the absence of muscle activity

“…To determine whether the influence of innervation and muscle activity on MHC-1 expression is species specific, we have compared the results obtained in different studies (Table 1). Table 1 indicates that the effects of denervation were globally similar between species (5,6,11,13,14,21,22,28,31,35,45,55,60). However, there are two notable exceptions.…”

“…Usually, P max and velocity of shortening are related to myosin ATPase activity and MHC protein expression (10). It should be noted that the aging process and spinal cord injury also modify maximal velocity of shortening without inducing any corresponding change in MHC-1 protein expression (15,35). Furthermore, the twitch kinetics were slower in denervated muscles (contraction and one-half relaxation times increased), indicating changes in the properties of the sarcoplasmic reticulum (41,45).…”

The length–tension relationship of human dorsiflexor and plantarflexor muscles after spinal cord injury

“…RTD is dependent on myosin ATPase activity and is directly related to the proportion of type IIb fibres. 12 Previous studies have shown that muscles undergo a fibre-type transformation towards a greater representation of type IIb fibres in vastus lateralis 1,13,14 and soleus muscles 2 after SCI. There is some suggestion that the degree of fibre-type transformation may be influenced by the amount of spasticity in a particular muscle after SCI.…”