Excitation-induced Ca21 uptake in rat skeletal muscle

Gissel, H., and T. Clausen. Excitation-induced Ca21 uptake in rat skeletal muscle. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R331–R339, 1999.—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 45Ca (154% above control after 240 min) and a progressive accumulation of Ca21 (85% above control after 240 min). In soleus, however, this treatment led to a small, but significant, increase in 45Ca uptake (30% above control after 180 min) but no significant accumulation of Ca21. In muscles mounted for isotonic contractions without any external load, electrical stimulation gave rise to a larger 45Ca uptake and accumulation of Ca21 in both EDL and soleus. These uptakes of Ca21 coincided with an accumulation of Na1. During isometric or isotonic contractions, stimulation at 40 Hz increased the initial (60 s) rate of 45Ca uptake in soleus muscle 15and 30-fold, respectively. The stimulation-induced increase in 45Ca uptake was only reduced by 17% by the Ca21-channel blockers nifedipine and verapamil but was blocked by tetrodotoxin. The initial rate of stimulation-induced 22Na and 45Ca uptake was correlated (r 5 0.80; P , 0.003). Stimulation of Na1 channels with veratridine increased 45Ca 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 Ca21, mediated by Na1 channels.