Excitation-induced Ca2+ uptake in rat skeletal muscle

In isolated rat extensor digitorum longus (EDL) muscle mounted for isometric contractions, chronic low-frequency electrical stimulation was found to lead to an increased uptake of Ca-45 (154% above control after 240 min) and a progressive accumulation of Ca2+ (85% above control after 240 min). In soleus, however, this treatment led to a small, but significant, increase in Ca-45 uptake (30% above control after 180 min) but no significant accumulation of Ca2+. In muscles mounted for isotonic contractions without any external load, electrical stimulation gave rise to a larger Ca-45 uptake and accumulation of Ca2+ in both EDL and soleus. These uptakes of Ca2+ coincided with an accumulation of Na+. During isometric or isotonic contractions, stimulation at 40 Hz increased the initial (60 s) rate of Ca-45 uptake in soleus muscle 15- and 30-fold, respectively. The stimulation-induced increase in Ca-45 uptake was only reduced by 17% by the Ca2+-channel blockers nifedipine and verapamil but was blocked by tetrodotoxin. The initial rate of stimulation-induced Na-22 and Ca-45 uptake was correlated (r = 0.80; P < 0.003). Stimulation of Na+ channels with veratridine increased Ca-45 uptake by 93 and 139% in soleus and EDL, respectively (P < 0.001), effects that were abolished by tetrodotoxin. The results indicate that in skeletal muscle, excitation induces a considerable influx of Ca2+, mediated by Na+ channels.