Developmental changes in diaphragm contractile properties

1993 ◽  
Vol 75 (2) ◽  
pp. 522-526 ◽  
Author(s):  
B. J. Moore ◽  
H. A. Feldman ◽  
M. B. Reid

The contractile properties of pre- and early postnatal respiratory muscles are incompletely understood. We examined the effects of development on isometric contractile properties, with an emphasis on properties at 37 degrees C. One-day-old (n = 10), 3-wk-old (n = 10), and adult (n = 10) rabbits were studied. Isometric contractile properties of costal diaphragm strips were measured in vitro by using direct stimulation. Twitch and maximal, i.e., fused, tetanic force production increased with strip dimension and with age. Maximal tetanic force developed per unit cross-sectional area (stress) was significantly decreased in muscle from 1-day olds, whereas it was greatest in muscle from 3-wk olds. Twitch stress was similar in all three groups. Only when the stimulus duration was prolonged did twitch and fused tetanic force achieve maximal values values for the 1-day-old and 3-wk-old strips, suggesting less effective excitation-contraction coupling in those muscles. We conclude that immature rabbit diaphragm has unique isometric contractile properties and stimulus parameter requirements that cannot be deduced from studies using mature diaphragm.

2002 ◽  
Vol 92 (3) ◽  
pp. 941-948 ◽  
Author(s):  
Wesley N. Smith ◽  
Amie Dirks ◽  
Takao Sugiura ◽  
Susan Muller ◽  
Phillip Scarpace ◽  
...  

Aging is associated with a decrease in diaphragmatic maximal tetanic force production (Po) in senescent rats. Treatment with the β2-agonist clenbuterol (CB) has been shown to increase skeletal muscle mass and Po in weak locomotor skeletal muscles from dystrophic rodents. It is unknown whether CB can increase diaphragmatic mass and Po in senescent rats. Therefore, we tested the hypothesis that CB treatment will increase specific Po (i.e., force per cross-sectional area) and mass in the diaphragm of old rats. Young (5 mo) and old (23 mo) male Fischer 344 rats were randomly assigned to one of the following groups ( n = 10/group): 1) young CB treated; 2) young control; 3) old CB treated; and 4) old control. Animals were injected daily with either CB (2 mg/kg) or saline for 28 days. CB increased ( P < 0.05) the mass of the costal diaphragm in both young and old animals. CB treatment increased diaphragmatic-specific Po in old animals (∼15%; P < 0.05) but did not alter ( P > 0.05) diaphragmatic-specific Po in young animals. Biochemical analysis indicated that the improved maximal specific Po in the diaphragm of CB-treated old animals was not due to increased myofibrillar protein concentration. Analysis of the myosin heavy chain (MHC) content of the costal diaphragm revealed a CB-induced increase ( P < 0.05) in type IIb MHC and a decrease in type I, IIa, and IIx MHC in both young and old animals. These data support the hypothesis that CB treatment can restore the age-associated decline in both diaphragmatic-specific Po and muscle mass.


1990 ◽  
Vol 69 (4) ◽  
pp. 1390-1396 ◽  
Author(s):  
E. Derom ◽  
S. Janssens ◽  
V. De Bock ◽  
M. Decramer

We examined the effects of theophylline on contractile properties and high-frequency fatigue of canine diaphragm in vitro. Eighteen diaphragm muscle bundles were obtained from 10 anesthetized dogs and equilibrated in oxygenated Krebs solution to 100, 200, or 300 mg/l theophylline. These bundles were compared with 18 matched control bundles from the contralateral hemidiaphragm. No statistically significant differences in twitch tension, tetanic tension, twitch-to-tetanus ratio, time to peak tension, or half-relaxation time were observed. Concentrations of 300 mg/l theophylline, however, significantly (P less than 0.05) increased force production at 10 Hz by 32%. A similar tendency was present at lower concentrations and exhibited a clear dose-response behavior. High-frequency fatigue was similar in control and theophylline-treated bundles. We conclude that supratherapeutic in vitro concentrations of theophylline do not increase maximal tetanic tension and do not protect against muscle fatigue but potentiate relative force production at low stimulation frequencies. This relatively small effect cannot be explained by poor diffusion of the drug in the muscle bundle, because theophylline concentrations in the muscle bath and in the muscle bundle were virtually identical. Moreover, it remains unclear whether this potentially beneficial effect can be achieved at in vivo attainable serum concentrations.


2000 ◽  
Vol 88 (6) ◽  
pp. 2054-2061 ◽  
Author(s):  
Leo M. A. Heunks ◽  
Aalt Bast ◽  
Cees L. A. van Herwaarden ◽  
Guido R. M. M. Haenen ◽  
P. N. Richard Dekhuijzen

Loading of skeletal muscles is associated with increased generation of oxidants, which in turn may impair muscle contractility. We investigated whether the load on the hamster diaphragm imposed by pulmonary emphysema induces oxidative stress, as indicated by glutathione oxidation, and whether the degree of glutathione oxidation is correlated with contractility of the diaphragm. In addition, the effect of 12 wk of treadmill exercise training on contractility and glutathione content in the normal (NH) and emphysematous hamster (EH) diaphragm was investigated. Training started 6 mo after elastase instillation. After the training period, glutathione content and in vitro contractility of the diaphragm were determined. Twitch force and maximal tetanic force were significantly reduced (by ∼30 and ∼15%, respectively) in EH compared with NH. In sedentary hamsters, the GSSG-to-GSH ratio was significantly elevated in the EH compared with the NH diaphragm. A significant inverse correlation was found between GSSG-to-GSH ratio and twitch force in the diaphragm ( P < 0.01). Training improved maximal tetanic force and reduced fatigability of the EH diaphragm but did not alter its glutathione content. In conclusion, 1) emphysema induces oxidative stress in the diaphragm, 2) training improves the contractile properties of the EH diaphragm, and 3) this improvement is not accompanied by changes in glutathione redox status.


2006 ◽  
Vol 101 (3) ◽  
pp. 898-905 ◽  
Author(s):  
Christopher L. Mendias ◽  
James E. Marcin ◽  
Daniel R. Calerdon ◽  
John A. Faulkner

Myostatin is a negative regulator of muscle mass. The impact of myostatin deficiency on the contractile properties of healthy muscles has not been determined. We hypothesized that myostatin deficiency would increase the maximum tetanic force (Po), but decrease the specific Po(sPo) of muscles and increase the susceptibility to contraction-induced injury. The in vitro contractile properties of extensor digitorum longus (EDL) and soleus muscles from wild-type ( MSTN+/+), heterozygous-null ( MSTN+/−), and homozygous-null ( MSTN−/−) adult male mice were determined. For EDL muscles, the Poof both MSTN+/−and MSTN−/−mice were greater than the Poof MSTN+/+mice. For soleus muscles, the Poof MSTN−/−mice was greater than that of MSTN+/+mice. The sPoof EDL muscles of MSTN−/−mice was less than that of MSTN+/+mice. For soleus muscles, however, no difference in sPowas observed. Following two lengthening contractions, EDL muscles from MSTN−/−mice had a greater force deficit than that of MSTN+/+or MSTN+/−mice, whereas no differences were observed for the force deficits of soleus muscles. Myostatin-deficient EDL muscles had less hydroxyproline, and myostatin directly increased type I collagen mRNA expression and protein content. The difference in the response of EDL and soleus muscles to myostatin may arise from differences in the levels of a myostatin receptor, activin type IIB. Compared with the soleus, the amount of activin type IIB receptor was approximately twofold greater in EDL muscles. The results support a significant role for myostatin not only in the mass of muscles but also in the contractility and the composition of the extracellular matrix of muscles.


2010 ◽  
Vol 298 (1) ◽  
pp. C149-C162 ◽  
Author(s):  
Nadège Zanou ◽  
Georges Shapovalov ◽  
Magali Louis ◽  
Nicolas Tajeddine ◽  
Chiara Gallo ◽  
...  

Skeletal muscle contraction is reputed not to depend on extracellular Ca2+. Indeed, stricto sensu , excitation-contraction coupling does not necessitate entry of Ca2+. However, we previously observed that, during sustained activity (repeated contractions), entry of Ca2+is needed to maintain force production. In the present study, we evaluated the possible involvement of the canonical transient receptor potential (TRPC)1 ion channel in this entry of Ca2+and investigated its possible role in muscle function. Patch-clamp experiments reveal the presence of a small-conductance channel (13 pS) that is completely lost in adult fibers from TRPC1−/−mice. The influx of Ca2+through TRPC1 channels represents a minor part of the entry of Ca2+into muscle fibers at rest, and the activity of the channel is not store dependent. The lack of TRPC1 does not affect intracellular Ca2+concentration ([Ca2+]i) transients reached during a single isometric contraction. However, the involvement of TRPC1-related Ca2+entry is clearly emphasized in muscle fatigue. Indeed, muscles from TRPC1−/−mice stimulated repeatedly progressively display lower [Ca2+]itransients than those observed in TRPC1+/+fibers, and they also present an accentuated progressive loss of force. Interestingly, muscles from TRPC1−/−mice display a smaller fiber cross-sectional area, generate less force per cross-sectional area, and contain less myofibrillar proteins than their controls. They do not present other signs of myopathy. In agreement with in vitro experiments, TRPC1−/−mice present an important decrease of endurance of physical activity. We conclude that TRPC1 ion channels modulate the entry of Ca2+during repeated contractions and help muscles to maintain their force during sustained repeated contractions.


1997 ◽  
Vol 200 (3) ◽  
pp. 523-529
Author(s):  
H P Buschman ◽  
W J van der Laarse ◽  
G J Stienen ◽  
G Elzinga

The origin of the threefold variation found previously in isometric force normalized to cross-sectional area of single fast-twitch tibialis anterior muscle fibres of the frog Rana temporaria was studied by using (1) a strictly defined stimulus protocol, and (2) influencing the condition of the frog using artificial hibernation. Variation in normalized force was found to be influenced by the length of the rest period between tetani. After a long rest (&gt; 6h), tetanic force production was less than for a tetanus produced after 1 h. The length of the rest period accounted for a factor of 1.24 of the total variation in normalized force. The condition of the frog also influenced normalized force production. Little variation in normalized force was observed between different fibres from the same animal, whereas a significant difference was found between animals. After artificial hibernation, force normalized to cross-sectional area remained unchanged, but force normalized to dry mass per unit length increased; the total variation increased from a factor of 1.37 to a factor of 1.64. Force normalized to muscle protein mass per unit length, however, was not affected by artificial hibernation. We conclude that variation in normalized tetanic force can be partly reduced by standardization of the stimulation protocol and normalization to protein content per unit length.


1989 ◽  
Vol 67 (1) ◽  
pp. 174-180 ◽  
Author(s):  
T. M. Murphy ◽  
R. W. Mitchell ◽  
J. S. Blake ◽  
M. M. Mack ◽  
E. A. Kelly ◽  
...  

We studied the effect of maturation on contractile properties of tracheal smooth muscle from seventeen 2-wk-old swine (2ws) and fifteen 10-wk-old swine (10ws) in situ and in vitro. The response to parasympathetic stimulation was studied in situ in isometrically fixed segments. Contraction was elicited at lower frequencies [half-maximal response to electrical stimulation (ES50) = 6.7 +/- 0.05 Hz] in 2ws than in 10ws (ES50 = 9.1 +/- 0.4 Hz; P less than 0.01). Despite substantial differences in morphometrically normalized cross-sectional area in 2ws (0.012 +/- 0.003 cm2) and 10ws (0.028 +/- 0.001 cm2; P less than 0.01), maximal active tension elicited by parasympathetic stimulation was similar (12.4 +/- 3.2 g/cm in 2ws vs. 13.3 +/- 2.3 g/cm in 10ws; P = NS). In separate in vitro studies in 25 tracheal smooth muscle strips from 10 swine, concentration-response curves generated with potassium-substituted Krebs solution (KCl) were similar in 2ws and 10ws. In 58 other strips (10 swine), maximal active force elicited with acetylcholine (ACh) in 2ws was significantly greater than for 10ws (P less than 0.001). Removal of the epithelium had no effect. However, cholinesterase inhibition with 10(-7) M physostigmine augmented the response to ACh in 10ws (P less than 0.02) but not 2ws. We demonstrate increased force generation and sensitivity to vagal stimulation in 2ws vs. 10ws, which corresponds to increased reactivity to ACh in vitro. The relative hyperresponsiveness in 2ws is specific for cholinergic response and is attenuated at least in part by maturation of the activity of acetylcholinesterase enzyme.


1984 ◽  
Vol 52 (6) ◽  
pp. 1131-1139 ◽  
Author(s):  
Y. Fukami

Active tetanic tension developed by stimulation of a nerve innervating single isolated muscle spindles of the cat was measured. The maximum tetanic force varied among spindles, ranging from 2.3 to 8.5 mg. For four spindles, the maximum tetanic force was converted into the force per unit cross-sectional area of nuclear chain and nuclear bag fibers. The results are discussed in terms of structural and functional complexities of the intrafusal fibers. The length-tension diagram of single isolated spindles showed maximum tetanic tension occurring at a spindle length longer than 1o, which was defined as the length beyond which passive tension starts to develop. This result, which appears to be different from the corresponding diagram for extrafusal muscle, is discussed in relation to the existing reports on the mechanical properties of intrafusal fibers. Spindle sensory response vs. tetanic tension was analyzed for single isolated spindles with two independent nerve supplies, one containing sensory and the other containing fusimotor axons. The results suggest that the static discharge rate of sensory endings may be linearly related, within the range examined, to the tetanic plateau tension of intrafusal fibers.


1990 ◽  
Vol 69 (3) ◽  
pp. 861-867 ◽  
Author(s):  
S. C. Kandarian ◽  
T. P. White

Hypotheses were tested that the deficit in maximum isometric force normalized to muscle cross-sectional area (i.e., specific Po, N/cm2) of hypertrophied muscle would return to control value with time and that the rate and magnitude of adaptation of specific force would not differ between soleus and plantaris muscles. Ablation operations of the gastrocnemius and plantaris muscles or the gastrocnemius and soleus muscles were done to induce hypertrophy of synergistic muscle left intact in female Wistar rats (n = 47) at 5 wk of age. The hypertrophied soleus and plantaris muscles and control muscles from other age-matched rats (n = 22) were studied from days 30 to 240 thereafter. Po was measured in vitro at 25 degrees C in oxygenated Krebs-Ringer bicarbonate. Compared with control values, soleus muscle cross-sectional area increased 41-15% from days 30 to 240 after ablation, whereas Po increased 11 and 15% only at days 60 and 90. Compared with control values, plantaris muscle cross-sectional area increased 52% at day 30, 40% from days 60 through 120, and 15% at day 240. Plantaris muscle Po increased 25% from days 30 to 120 but at day 240 was not different from control value. Changes in muscle architecture were negligible after ablation in both muscles. Specific Po was depressed from 11 to 28% for both muscles at all times. At no time after the ablation of synergistic muscle did the increased muscle cross-sectional area contribute fully to isometric force production.


1993 ◽  
Vol 74 (1) ◽  
pp. 326-332 ◽  
Author(s):  
A. P. Gauthier ◽  
R. E. Faltus ◽  
P. T. Macklem ◽  
F. Bellemare

It has been established that the in vivo operating length of the diaphragm corresponds to a wide range of the ascending limb of its length-tetanic force relationship. To investigate the length-dependent effects of fatigue on maximum force production, we constructed length-tetanic force relationships of rat costal diaphragm strips in vitro before and after fatigue induced by repetitive supramaximal electrical field stimulations at optimal length. Two levels of fatigue were studied (i.e., force reductions of 40 and 65% at optimal length). Results indicate that fatigue, when evaluated with high-frequency stimulations, causes a proportionately larger decrease in tetanic force at short muscle lengths as seen by a smaller control force-to-fatigue force ratio and an apparent shift in the length at which active force is zero. A possible explanation for the results obtained is failure of propagation of membrane depolarization into the t-tubule system at short muscle lengths, which is aggravated by fatigue evaluated by high-frequency stimulation.


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