Effects of external calcium on contractile responses in rat extensor digitorum longus muscles after sciatic nerve injury at birth

Two types of nerve lesions were performed at birth in rat extensor digitorum longus muscle: sciatic nerve transection (group A) and sciatic nerve crush allowing further reinnervation (group B). Contractile responses were then studied at different times after the denervation (7, 14, 30, and 60 days) and compared with control. Sixty days after the intervention, twitch and tetanic tensions remained dependent upon the extracellular Ca²⁺ concentration ([Ca]_o) both in groups A and B. However, the depression of tensions following Ca²⁺ withdrawal was more important in group A. Sixty days after birth, in the presence of a Ca²⁺ channel blocker, Cd²⁺ (2 mmol L⁻¹), a depression of the twitch tension was observed in group A (similarly to control 1–7 days postnatal muscles), whereas Cd²⁺ potentiated twitch tension in group B (similarly to control 14–60 days postnatal muscles). After glycerol treatment (detubulating procedure) performed in 60-day-old muscles, twitch tension was abolished in group B and control, whereas twitch tension was potentiated in group A. Thus, in developing muscles, neural control could be involved in the dependence of contractility toward [Ca]_o. These results may be relevant for the understanding of the contractile properties of neuromuscular disorders with early onset. © 1996 John Wiley & Sons, Inc.     

Aging impairs regulation of ryanodine receptors from extensor digitorum longus but not soleus muscles

ABSTRACT: Introduction: Because impaired excitation‐contraction coupling and reduced sarcoplasmic reticulum (SR) Ca²⁺ release may contribute to the age‐associated decline in skeletal muscle strength, we investigated the effect of aging on regulation of the skeletal muscle isoform of the ryanodine receptor (RyR1) by physiological channel ligands. Methods: [³H]Ryanodine binding to membranes from 8‐ and 26‐month‐old Fischer 344 extensor digitorum longus (EDL) and soleus muscles was used to investigate the effects of age on RyR1 modulation by Ca²⁺ and calmodulin (CaM). Results: Aging reduced maximal Ca²⁺‐stimulated binding to EDL membranes. In 0.3 μM Ca²⁺, age reduced binding and CaM increased binding to EDL membranes. In 300 μM Ca²⁺, CaM reduced binding, but the age effect was not significant. Aging did not affect Ca²⁺ or CaM regulation of soleus RyR1. Discussion: In aged fast‐twitch muscle, impaired RyR1 Ca²⁺ regulation may contribute to lower SR Ca²⁺ release and reduced muscle function. Muscle Nerve 57 : 1022–1025, 2018     

A fractal characterization of the type II fiber distribution in the extensor digitorum longus and soleus muscles of the adult rat

A method is proposed for the quantitative characterization of fiber type spatial distribution by means of the (correlation) fractal dimension. The method is applied to type II fiber distributions of the soleus and extensor digitorum longus muscles of the adult rat. The results obtained suggest that these distributions have fractal properties with a strong tendency for spreading, more pronounced in soleus muscle. The density of muscle fibers or the age do not seem to alter the features of the distribution. Computer-generated random patterns have virtually the same fractal dimension as the extensor digitorum longus distributions but fail to approximate those of the soleus muscle. This fractal method could find application as an alternative in the quantitative assessment of the fiber type grouping. © 1995 John Wiley & Sons, Inc.     

Anti‐dyskinetic mechanisms of amantadine and dextromethorphan in the 6‐OHDA rat model of Parkinson’s disease: role of NMDA vs. 5‐HT1A receptors

Amantadine and dextromethorphan suppress levodopa (L‐DOPA)‐induced dyskinesia (LID) in patients with Parkinson’s disease (PD) and abnormal involuntary movements (AIMs) in the unilateral 6‐hydroxydopamine (6‐OHDA) rat model. These effects have been attributed to N‐methyl‐d ‐aspartate (NMDA) antagonism. However, amantadine and dextromethorphan are also thought to block serotonin (5‐HT) uptake and cause 5‐HT overflow, leading to stimulation of 5‐HT_1A receptors, which has been shown to reduce LID. We undertook a study in 6‐OHDA rats to determine whether the anti‐dyskinetic effects of these two compounds are mediated by NMDA antagonism and/or 5‐HT_1A agonism. In addition, we assessed the sensorimotor effects of these drugs using the Vibrissae‐Stimulated Forelimb Placement and Cylinder tests. Our data show that the AIM‐suppressing effect of amantadine was not affected by the 5‐HT_1A antagonist WAY‐100635, but was partially reversed by the NMDA agonist d ‐cycloserine. Conversely, the AIM‐suppressing effect of dextromethorphan was prevented by WAY‐100635 but not by d ‐cycloserine. Neither amantadine nor dextromethorphan affected the therapeutic effects of L‐DOPA in sensorimotor tests. We conclude that the anti‐dyskinetic effect of amantadine is partially dependent on NMDA antagonism, while dextromethorphan suppresses AIMs via indirect 5‐HT_1A agonism. Combined with previous work from our group, our results support the investigation of 5‐HT_1A agonists as pharmacotherapies for LID in PD patients.