Inhibition of carbonic anhydrases in type I muscle fibers influences contractility

1989 ◽  
Vol 67 (6) ◽  
pp. 645-649 ◽  
Author(s):  
C. Côté ◽  
D. Tremblay ◽  
H. Riverin ◽  
P. Frémont ◽  
P. A. Rogers

We tested the effects of inhibiting the carbonic anhydrase activity of rat soleus and extensor digitorum longus muscles on the isometric contractile properties and the resistance to fatigue. SOL and EDL muscles from female rats were incubated in vitro in the presence of methazolamide, a specific inhibitor of carbonic anhydrase, before determining their contractile properties. Methazolamide had no effects on the contractile properties of the soleus muscle (10−5 or 10−3 M) and extensor digitorum longus (10−3 M), except for the half-relaxation time of the soleus muscle which increased significantly. Values for half-relaxation time were significantly increased with both concentrations of the inhibitor. Muscles were then submitted to a fatigue protocol lasting 30 min. During the fatigue test, no significant difference was observed between control and 10−5 M methazolamide soleus muscles. In presence of 10−3 M methazolamide however, the soleus muscle showed a significantly increased resistance to fatigue compared with control preparations. No significant effect was observed with the extensor digitorum longus muscle exposed to 10−3 M methazolamide. Results are discussed in terms of the presence of two different isoforms of carbonic anhydrase that may be associated with calcium uptake and energy metabolic processes, respectively.Key words: carbonic anhydrase, skeletal muscle, contraction, fatigue, soleus muscle.

1982 ◽  
Vol 30 (12) ◽  
pp. 1275-1288 ◽  
Author(s):  
D A Riley ◽  
S Ellis ◽  
J Bain

Carbonic anhydrase (CA) activities were studied in soluble extracts and cryostat sections of skeletal muscles from prepubertal and postpubertal rats. Acetazolamide inhibition was utilized to distinguish between activities of the acetazolamide-sensitive (CA I and II) and acetazolamide-resistant (CA III) forms of the enzyme. The inhibition studies indicated that fast-twitch oxidative-glycolytic muscle fibers contained both the sensitive and resistant forms of CA. Acetazolamide-sensitive activity was localized within muscle fibers, axons, myelin, and capillaries. Axoplasmic staining was restricted to subpopulations of myelinated axons in both the dorsal and ventral roots. Soleus muscles exhibited significantly greater activity of CA III than extensor digitorum longus muscles at all ages examined. CA III was richest in slow-twitch oxidative and intrafusal fibers. During puberty, soleus muscle fibers matured and converted from fast-twitch oxidative-glycolytic to slow-twitch oxidative fibers. There was a shift from the sensitive to the resistant form of CA; CA III activity increased about sevenfold. This activity peaked earlier in the muscles of female rats than male rats. These results demonstrated a complex distribution of CA isozymes in the neuromuscular system and pointed out that isozyme content depends on both the type of muscle and the age and sex of the animal.


1980 ◽  
Vol 238 (3) ◽  
pp. C120-C126 ◽  
Author(s):  
J. A. Faulkner ◽  
J. H. Niemeyer ◽  
L. C. Maxwell ◽  
T. P. White

Following autologous transplantation of whole extensor digitorum longus (EDL) muscles of cats into the EDL site, we investigated the degree and time course of restoration of contractile properties of autografts toward control values. Isometric and isotonic contractile properties of 66 autografted EDL muscles were measured in situ from 40 to 440 days following transplantation. The control value for maximum tetanus tension (P0) was 27 N. The mean P0 for the autografts increased from 2% of control 40 days after transplantation to 26% 440 days after transplantation. When P0 was normalized per square centimeter of muscle fiber cross-sectional area, no significant difference was observed between the P0 of autografts (28 N/cm2) and controls. Compared to controls, autografts 40-179 days following transplantation had slower time to peak twitch tensions, half-relaxation times, and maximum velocities of shortening and smaller twitch-tetanus tension ratios. Between 180 and 440 days after transplantation, values for autografts approached control values. Autografts fatigued more than twice as rapidly as controls.


1996 ◽  
Vol 148 (3) ◽  
pp. 501-507 ◽  
Author(s):  
S B Bowes ◽  
N C Jackson ◽  
D Papachristodoulou ◽  
A M Umpleby ◽  
P H Sönksen

Abstract The net catabolic effect of glucocorticoids on protein metabolism is well documented but the acute and chronic effect of glucocorticoids on protein breakdown remains controversial. In the present studies protein breakdown was measured by the release of tyrosine from the isolated soleus and extensor digitorum longus (EDL) muscles of control rats and rats treated with corticosterone (10 mg/100 g body weight/day) for 5 days. The effect of corticosterone in arresting growth was confirmed since corticosterone-treated rats weighed significantly less than control rats after 2, 3, 4 and 5 days of treatment (P<0·001). Furthermore, the weights of soleus and EDL muscles from corticosterone-treated rats were significantly reduced (P<0·001, at least P<0·05 respectively) compared with muscles from control rats on days 3–5. In the EDL muscle tyrosine release was significantly elevated after corticosterone treatment for 2 days (257 ± 21 nmol/g tissue/h, P<0·05), 3 days (205 ± 9 nmol/g tissue/h, P<0·01), 4 days (255 ± 20 nmol/g tissue/h, P<0·005) and 5 days (218 ± 8 nmol/g tissue/h, P<0·05) compared with EDL from control rats (192 ± 13, 171 ± 7, 187 ± 7, 180 ± 12 nmol/g tissue/h respectively). In the soleus muscle, tyrosine release was significantly elevated after corticosterone treatment for 2 days (226 ± 14 nmol/g tissue/h, P<0·001), 3 days (223 ± 16 nmol/g tissue/h, P<0·001) and 4 days (199 ± 10 nmol/g tissue/h, P<0·001) compared with control rats (158 ± 7, 132 ± 6 and 153 ± 7 nmol/g tissue/h respectively). After 5 days there was no significant difference in tyrosine release from soleus muscle between corticosterone-treated (176 ± 15 nmol/g tissue/h) and control rats (157 ± 6 nmol/g tissue/h). Plasma glucose concentrations were not significantly different in rats treated with corticosterone and control rats whilst insulin levels were significantly raised in the corticosterone-treated rats on all days compared with control rats (P<0·05 on day 1; P<0·001 on days 2, 3, 4 and 5). It is suggested that insulin may have prevented hyperglycaemia developing in the corticosterone-treated rats. Results from these studies indicate that the acute effect of glucocorticoids is to increase muscle proteolysis but this is not maintained with longer-term treatment. Journal of Endocrinology (1996) 148, 501–507


1995 ◽  
Vol 269 (5) ◽  
pp. R1154-R1162 ◽  
Author(s):  
A. D. Kriketos ◽  
D. A. Pan ◽  
J. R. Sutton ◽  
J. F. Hoh ◽  
L. A. Baur ◽  
...  

Insulin resistance in skeletal muscle is associated with 1) relative increases in the proportion of glycolytic and fast-twitch muscle fibers and decreases in the proportion of more oxidative fibers and 2) a higher proportion of the saturated fatty acids in membrane structural lipids. Exercise is known to improve insulin action. The aims of the current studies were 1) to investigate the relationship between muscle fiber type and membrane fatty acid composition and 2) to determine how voluntary exercise might influence both variables. In sedentary Wistar rats in experiment 1, increased amounts of unsaturated fatty acids were found in the more oxidative insulin-sensitive red quadriceps and soleus muscles, whereas reduced levels of polyunsaturated fatty acids were found in primarily glycolytic white quadriceps muscles. In experiment 2, voluntary running-wheel exercise by adult female rats over 45 days resulted in reduced proportions of type IIb fibers (P = 0.01) and increased proportions of type IIa/IIx fibers (P = 0.03) in extensor digitorum longus muscle. The magnitude of these changes was related to the distance run (r = -0.73, P = 0.04; r = 0.79, P = 0.02, respectively). Exercise significantly increased oxidative capacity, as assessed by the proportion of intensely NADH-stained fibers (P = 0.0004) and citrate synthase (P = 0.003) and hexokinase (P = 0.04) activities. Citrate synthase activity was also increased by exercise in soleus muscle, where, as expected, no fiber type changes were detected. No significant differences in the fatty acid profile of soleus and extensor digitorum longus were found between groups.(ABSTRACT TRUNCATED AT 250 WORDS)


1996 ◽  
Vol 43 (4) ◽  
pp. 693-700 ◽  
Author(s):  
J Moraczewski ◽  
E Piekarska ◽  
M Zimowska ◽  
M Sobolewska

Calpains--non-lysosomal intracellular calcium-activated neutral proteinases, form a family consisting of several distinct members. Two of the isoenzymes: mu (calpain I) and m (calpain II) responded differently to the injury during complete regeneration of Extensor digitorum longus (EDL) muscle and partial regeneration of Soleus muscle. In the crushed EDL the level of m-calpain on the 3rd and 7th day of regeneration was higher than in non-operated muscles, whereas the activity of this calpain in injured Soleus decreased. The level of mu-calpain in EDL oscillated irregularly during regeneration whereas in Soleus of both injured and contralateral muscles its level rapidly rose. Our results support the hypothesis that m-calpain is involved in the process of fusion of myogenic cells whereas mu-calpain plays a significant but indirect role in muscle regeneration.


1999 ◽  
Vol 276 (2) ◽  
pp. R559-R565 ◽  
Author(s):  
Claude H. Côté ◽  
Fabrisia Ambrosio ◽  
Guylaine Perreault

Carbonic anhydrase (CA) III is very abundant in type I skeletal muscle, but its function is still debated. Our aims were to examine CA III expression during growth and determine whether the effects of CA inhibition previously observed in adult muscles could be seen in younger rats in which CA III levels are lower. CA III content and activity were measured in soleus muscles from 10- to 100-day-old rats, and the influence of CA inhibitor on fatigue and hexosemonophosphate content was quantified in vitro. CA III activity and content increased fivefold between 10 and 100 days of age. Data analysis revealed that the influence of CA inhibitor on fatigue was to some extent positively and linearly related to the level of CA III activity. Hexosemonophosphate accumulation with CA inhibition also became more significant with age. In conclusion, CA III level in soleus muscle does not stabilize before 3 mo after birth; data also confirm that the effects of CA inhibitors are due to inhibition of the CA III isoform.


1991 ◽  
Vol 81 (2) ◽  
pp. 267-270 ◽  
Author(s):  
R. G. Cooper ◽  
C. M. Taylor ◽  
J. J. Choo ◽  
J. B. Weiss

1. Capillary density is greater in skeletal muscles comprised of predominantly oxidative (type I) fibres than in those comprised of mainly glycolytic (type II) fibres. In order to investigate further the angiogenic mechanisms involved in muscle capillarization, endothelial-cellstimulating angiogenic factor activities in various rodent skeletal muscles were compared. 2. Eleven untrained adult male Wistar rats were killed and the predominantly oxidative (type I) muscles, soleus and heart, the predominantly glycolytic (type II) muscle, extensor digitorum longus, and the mixed-fibre muscle, gastrocnemius, were removed. Each sample was separately homogenized and centrifuged and the supernatants were diafiltered to isolate the low-molecular-mass fraction containing endothelial-cell-stimulating angiogenic activity. This was assayed for its ability to activate latent collagenase and was expressed as units, where 1 unit represents the percentage activation of the enzyme h−1 (mg of protein in the supernatant)−1. 3. The results (medians and ranges) demonstrated significantly greater endothelial-cell-stimulating angiogenic factor activity in extensor digitorum longus muscle (2.14 units, 0.62–2.87 units, n = 13) than in soleus (0.82 units, 0.59–1.79 units, n = 15), gastrocnemius (0.34 units, 0.28–0.40 units, n = 4) or heart (0.43 units, 0.16–0.52 units, n = 11) (P< 0.01 for each) muscle. 4. These findings suggest that endothelial-cell-stimulating angiogenic activity in muscle is either inversely or not related to the local capillary density, which may be at or near a maximum in physiologically contracting, predominantly oxidative muscles.


1987 ◽  
Vol 65 (6) ◽  
pp. 1205-1212 ◽  
Author(s):  
John M. Kennedy ◽  
Franz S. F. Mong ◽  
James L. Poland

The metabolic integrity of fully regenerated transplants was investigated by measuring induced changes in glycogen concentration. The extensor digitorum longus and the soleus muscles were cross transplanted: the extensor digitorum longus into the soleus muscle bed (SOLT) and the soleus muscle into the extensor digitorum longus bed (EDLT). The histochemical fiber type distribution of the regenerated muscles was determined and was found to transform in cross-transplanted EDLT and SOLT. After transplantation and regeneration, both muscles had initially low glycogen concentrations. However, the EDLT glycogen concentration was not significantly different from that of the contralateral extensor digitoium longus control muscle after 60 days. In the SOLT, glycogen gradually increased but remained less than in the contralateral soleus control muscle. SOLT and control soleus muscles responded with a significant glycogen depletion to an epinephrine dose two orders of magnitude less than the lowest dose affecting glycogen levels in EDLT and extensor digitorum longus muscles. These results indicate that transplanted muscles are capable of regenerating normal glycogenolytic responses and that the sensitivity of the response observed depends on the site of transplantation and is related to the type of innervation and histochemical fiber type.


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