The action of dantrolene sodium on individual fast and slow motor units of the rat anaesthetized with urethane

Leslie, G. C.; Part, N. J.

doi:10.1111/j.1476-5381.1984.tb10086.x

Cited by 5 publications

(4 citation statements)

References 15 publications

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“…In soleus muscle, neither 5 nor 20 M dantrolene reduced the initial tetanic force, although both drug concentrations were effective in reducing twitch tension. The lower ability of dantrolene to affect tetanus tension with respect to twitch tension was also noted by others (15). Thus, in soleus muscle, dantrolene appears less effective in affecting SR Ca 2ϩ release under tetanic stimulation.…”

Section: Discussionsupporting

confidence: 67%

Effects of modulators of sarcoplasmic Ca²⁺ release on the development of skeletal muscle fatigue

Germinario¹,

Esposito²,

Megighian³

et al. 2004

Journal of Applied Physiology

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The reduced release of Ca2+ from sarcoplasmic reticulum (SR) is considered a major determinant of muscle fatigue. In the present study, we investigated whether the presence of dantrolene, an established inhibitor of SR Ca2+ release, or caffeine, a drug facilitating SR Ca2+ release, modifies muscle fatigue development. Accordingly, the effects of Ca2+ release modulators were analyzed in vitro in mouse fast-twitch [extensor digitorum longus (EDL)] and slow-twitch (soleus) muscles, fatigued by repeated short tetani (40 Hz for 300 ms, 0.5 s(-1) in soleus and 60 Hz for 300 ms, 0.3 s(-1) in EDL, for 6 min). Caffeine produced a substantial increase of tetanic tension of both EDL and soleus muscles, whereas dantrolene decreased tetanic tension only in EDL muscle. In both EDL and soleus muscles, 5 microM dantrolene did not affect fatigue development, whereas 20 microM dantrolene produced a positive staircase during the first 3 min of stimulation in EDL muscle and a slowing of fatigue development in soleus muscle. The development of the positive staircase was abolished by the addition of 15 microM ML-7, a selective inhibitor of myosin light chain kinase. On the other hand, caffeine caused a larger and faster loss of tension in both EDL and soleus muscles. The results seem to indicate that the changes in fatigue profile induced by caffeine or dantrolene are mainly due to the changes in the initial tetanic tension caused by the drugs, with the resulting changes in the level of contraction-dependent factors of fatigue, rather than to changes in the SR Ca2+ release during fatigue development.

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Section: Discussionsupporting

confidence: 67%

Effects of modulators of sarcoplasmic Ca²⁺ release on the development of skeletal muscle fatigue

Germinario¹,

Esposito²,

Megighian³

et al. 2004

Journal of Applied Physiology

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“…Comparison of the discharge frequencies recorded in this work with the previously examined frequency-related reponse of the motor units to dantrolene sodium (Leslie & Part, 1984) shows that the increase was not sufficient, to spare the muscle from the action of the drug. As the tension of the muscle is so well maintained in the presence of dantrolene sodium, recruitment of additional motor units must play a very important role in minimising tension decrease.…”

Section: Discussionmentioning

confidence: 90%

The effect of dantrolene sodium on the discharge of alpha and gamma motoneurones to the soleus muscle in the decerebrate rat

Farquhar

Part

1988

British J Pharmacology

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The effects of intravenous infusion of the direct acting muscle relaxant, dantrolene sodium (5 mg kg−1), on tension, integrated EMG, soleus muscle motor unit discharge frequency and gamma nerve fibre discharge were measured in the decerebrate rat. Dantrolene sodium did not have any detectable direct effect upon the discharge of the gamma nerve fibres. The soleus muscle of the decerebrate preparations exhibited spontaneous tension and reflex responses. With the muscle held at constant length, dantrolene sodium caused an increase in the integrated EMG in 15 out of 18 experiments and a decrease in muscle tension in 15 out of 17. The results from these experiments showed great variability. Dantrolene sodium caused a slight reduction in the tension response to tonic stretch; this was accompanied by an increase in the integrated EMG. Dantrolene sodium also caused a shift in the relationship between tension and integrated EMG during the phasic component of the stretch reflex, with a greater integrated EMG being associated with a reduced tension. Motor unit discharge frequencies were found to increase but not sufficiently to overcome the action of dantrolene sodium. It is concluded that motor unit recruitment must play an important role in the compensation for the muscle weakening action of dantrolene sodium.

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“…Dantrolene is a chemical agent that acts to inhibit the release of Ca 2+ from the sarcoplasmic reticulum for each stimulating pulse (Ellis & Carpenter 1972, Desmedt & Hainaut 1977, Leslie & Part 1984). Specifically, it targets the skeletal muscle ryanodine receptors inhibiting stimulation‐induced release of Ca 2+ (Zhao et al.…”

mentioning

confidence: 99%

Dantrolene, like fatigue, has a length‐dependent effect on submaximal force–length relationships of rat gastrocnemius muscle

2007

Acta Physiologica

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The action of dantrolene sodium on individual fast and slow motor units of the rat anaesthetized with urethane

Abstract: 1 Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a vehicle of 5 % mannitol taken to pH 10 with NaOH.

Cited by 5 publications

References 15 publications

Effects of modulators of sarcoplasmic Ca²⁺ release on the development of skeletal muscle fatigue

Effects of modulators of sarcoplasmic Ca²⁺ release on the development of skeletal muscle fatigue

The effect of dantrolene sodium on the discharge of alpha and gamma motoneurones to the soleus muscle in the decerebrate rat

Dantrolene, like fatigue, has a length‐dependent effect on submaximal force–length relationships of rat gastrocnemius muscle

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The action of dantrolene sodium on individual fast and slow motor units of the rat anaesthetized with urethane

Abstract: 1 Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a vehicle of 5 % mannitol taken to pH 10 with NaOH.

Cited by 5 publications

References 15 publications

Effects of modulators of sarcoplasmic Ca2+ release on the development of skeletal muscle fatigue

Effects of modulators of sarcoplasmic Ca2+ release on the development of skeletal muscle fatigue

The effect of dantrolene sodium on the discharge of alpha and gamma motoneurones to the soleus muscle in the decerebrate rat

Dantrolene, like fatigue, has a length‐dependent effect on submaximal force–length relationships of rat gastrocnemius muscle

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Effects of modulators of sarcoplasmic Ca²⁺ release on the development of skeletal muscle fatigue

Effects of modulators of sarcoplasmic Ca²⁺ release on the development of skeletal muscle fatigue