We hypothesized that inactivity effects on diaphragm muscle contractile and morphometric properties are attenuated if phrenic motoneurons are also inactive. Three models of rat diaphragm inactivity were compared: 1) spinal isolation; 2) tetrodotoxin (TTX) nerve blockade; and 3) denervation (Dnv). Motoneuron and muscle fiber inactivities were matched only in spinal isolated animals. After 2 wk, maximum tetanic force decreased in all three groups compared with control group but to a greater extent in TTX and Dnv animals. Fatigue resistance improved, and maximum unloaded shortening velocity slowed only in TTX and Dnv groups. Type IIa fiber proportions decreased in all three groups, and type IIx fiber proportions increased in TTX and Dnv animals. Type I fiber cross-sectional area increased in all three groups but to a greater extent in TTX and Dnv animals. Type IIa fibers hypertrophied, whereas type IIx and IIb fibers atrophied only in TTX and Dnv groups. These results support the hypothesis that muscle adaptations to prolonged inactivity are attenuated when muscle fiber and motoneuron inactivities are matched.

We hypothesized that metabolic adaptations to muscle inactivity are most pronounced when neurotrophic influence is disrupted. In rat diaphragm muscle (Dia(m)), 2 wk of unilateral denervation or tetrodotoxin nerve blockade resulted in a reduction in succinate dehydrogenase (SDH) activity of type I, IIa, and IIx fibers (approximately 50, 70, and 24%, respectively) and a decrease in SDH variability among fibers (approximately 63%). In contrast, inactivity induced by spinal cord hemisection at C2 (ST) resulted in much less change in SDH activity of type I and IIa fibers (approximately 27 and 24%, respectively) and only an approximately 30% reduction in SDH variability among fibers. Actomyosin adenosinetriphosphatase (ATPase) activities of type I, IIx, and IIb fibers in denervated and tetrodotoxin-treated Dia(m) were reduced by approximately 20, 45, and 60%, respectively, and actomyosin ATPase variability among fibers was approximately 60% lower. In contrast, only actomyosin ATPase activity of type IIb fibers was reduced (approximately 20%) in ST Dia(m). These results suggest that disruption of neurotrophic influence has a greater impact on muscle fiber metabolic properties than inactivity per se.

The relationship between muscle fibre composition and fibre conduction velocity was investigated in 19 male track athletes, 12 sprinters and 7 distance runners, aged 20-24 years, using needle biopsy samples from vastus lateralis. Cross sectional areas of the fast twitch (FT) and slow twitch (ST) fibres were determined by histochemical analysis. The percentage of FT fibre areas ranged from 22.6 to 93.6%. Sprinters had a higher percentage of FT fibres than distance runners. Muscle fibre conduction velocity was measured with a surface electrode array placed along the muscle fibres, and calculated from the time delay between 2 myoelectric signals recorded during a maximal voluntary contraction. The conduction velocity ranged from 4.13 to 5.20 m.s-1. A linear correlation between conduction velocity and the relative area of FT fibres was statistically significant (r = 0.84, p less than 0.01). This correlation indicates that muscle fibre composition can be estimated from muscle fibre conduction velocity measured noninvasively with surface electrodes.

In chronic kidney disease (CKD), progressive nephron loss causes glomerular sclerosis, as well as tubulointerstitial fibrosis and progressive tubular injury. In this study, we aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage. A discovery set of renal biopsies were obtained from 48 patients with histopathologically confirmed CKD, and gene expression profiles were determined by microarray analysis. The results indicated that hepatitis A virus cellular receptor 1 (also known as Kidney Injury Molecule-1, KIM-1), lipocalin 2 (also known as neutrophil gelatinase-associated lipocalin, NGAL), SRY-box 9, WAP four-disulfide core domain 2, and NK6 homeobox 2 were differentially expressed in CKD. Their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury, determined by histopathological examination. The expression of these 5 genes was also increased as kidney damage progressed in a rodent unilateral ureteral obstruction model of CKD. We calculated a molecular score using the microarray gene expression profiles of the biopsy specimens. The composite area under the receiver operating characteristics curve plotted using this molecular score showed a high accuracy for diagnosing tubulointerstitial fibrosis and tubular cell damage. The robust sensitivity of this score was confirmed in a validation set of 5 individuals with CKD. These findings identified novel molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney.

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