Changes in Na+, K+-adenosinetriphosphatase, citrate synthase and K+ in sheep skeletal muscle during immobilization and remobilization

Abstract

The K+ balance and muscle activity seem to interact in a complex way with regard to regulating the muscle density of Na(+)-K+ pumps. The effect of immobilization was examined in ten sheep that had low muscle K+ content. Three additional sheep served as untreated controls. After being brought from pasture to sheep stalls one hindlimb was immobilized in a plaster splint for 9 weeks, and in five of the animals remobilization was carried out for a further 9 weeks. The weight bearing of the leg in plaster was recorded by a force plate. Open muscle biopsies from the vastus lateralis muscle were obtained before the study, after 9 weeks of immobilization, and after another 9 weeks of remobilization. The Na(+)-K+ pump density was measured as [3H]-ouabain binding to intact tissue, and citrate synthase activity was measured in tissue homogenate. The tissue content of K+ was measured in fat-free dried tissue. Muscle K+ content increased linearly by almost 70% through the 18-week period independent of intervention. Immobilization reduced thigh circumference by 8% (P < 0.05). A slight decrease in the area of type I fibres at 9 weeks and a slight increase at 18-weeks was found. The [3H]-ouabain binding was reduced by 39% and 22% in the immobilized and control legs, respectively, whereas citrate synthase activity was reduced by about 30% in both legs after 9 weeks of immobilization. During remobilization both the [3H]-ouabain binding and the citrate synthase activity increased to the same level as in the control animals. The plaster cast significantly reduced mass bearing of the immobilized leg, and a corresponding reduction in muscle activity must be assumed to have occurred in both legs as judged from citrate synthase activity. We concluded from this study that the reduction in the [3H]-ouabain binding during immobilization independent of an increase in muscle K+ content points to muscle activity as a strong stimulus for control of Na(+)-K+ pump density.

Na+,K+‐ATPase concentration and fiber type distribution after spinal cord injury

“…Unfortunately, it is unclear whether participants in that study also suffered significant deficiencies to their skeletal muscle (such as reductions in fiber area), although further work by that group has shown that chronic heart failure induces reductions in capillary density and a higher predominance of type IIx fibers. 11 In other studies, 23,24 and the present study, the skeletal muscles of the participants were certainly affected as evidenced by accompanying muscle atrophy. The fact that skeletal muscle Na ϩ ,K ϩ -ATPase reductions were greater in the present study than in the two aforementioned studies 23,24 suggests that functional denervation, per se, has a specifically devastating effect on Na ϩ ,K ϩ -ATPase expression in addition to the effects of disuse alone.…”

“…11 In other studies, 23,24 and the present study, the skeletal muscles of the participants were certainly affected as evidenced by accompanying muscle atrophy. The fact that skeletal muscle Na ϩ ,K ϩ -ATPase reductions were greater in the present study than in the two aforementioned studies 23,24 suggests that functional denervation, per se, has a specifically devastating effect on Na ϩ ,K ϩ -ATPase expression in addition to the effects of disuse alone.…”

“…For example, Leivseth and Reikeras 24 examined the Na ϩ ,K ϩ -ATPase concentration in patients with impingement syndrome of the shoulder and found a 26.6% reduction in the affected deltoid compared to the unaffected deltoid. Likewise, Jebens and colleagues 23 found a 39% reduction in Na ϩ ,K ϩ -ATPase concentration in the vastus lateralis of sheep following leg immobilization for 9 weeks. Conversely, Green and colleagues 19 found no difference between the Na ϩ ,K ϩ -ATPase concentration in the vastus lateralis of patients with chronic heart failure (a condition associated with significant skeletal muscle deficiencies) and healthy age-matched controls.…”

“…12,17 The Na ϩ ,K ϩ -ATPase also exhibits a great deal of plasticity as it is upregulated in human skeletal muscle following both endurance 18,20,25 and sprint training, 27 and downregulated in animal muscle following denervation 9 or immobilization. 23 Considering its role in fatigue resistance and its plasticity, it is reasonable to suggest that downregulation of the Na ϩ ,K ϩ -ATPase following complete SCI may contribute to the increased fatigability of paralyzed muscle.…”

Influence of chronic and acute spinal cord injury on skeletal muscle Na+-K+-ATPase and phospholemman expression in humans

“…Leg immobilization in sheep for 9 wk is associated with a 39% reduction in Na ϩ -K ϩ -ATPase abundance in the vastus lateralis muscle (28). In rats, [ 3 H]ouabain binding capacity in soleus muscle is decreased 22% after 7 days of denervation (11).…”