[Increased activity of sarcoplasmic reticulum Ca(2+)-ATPase in soleus of hyperthyroid rat accelerates fatigue during...

The elevated plasma level of thyroxin and/or triiodothyronine in hyperthyroidism not only induces a transition from the innervated slow-twitch muscle fibers to fast-twitch fibers, but also changes the contractile function in transition muscle fibers. So the muscle weakness of thyrotoxic myopathy would relate to alteration in fatigability of tetanic contraction in muscles, especially in slow-twitch fibers. The aim of the present study was to observe the extent of fatigue of soleus in 4-week hyperthyroid rats and elucidate its underlying mechanism. The isolated soleus muscle strips were perfused in Krebs-Henseleit solution with or without an inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), cyclopiazonic acid (CPA). The contractile function of soleus was observed in twitch and intermittent tetanic contraction. The body weight in 4-week hyperthyroid rats decreased as compared with that in the control group [(292±13) g vs (354±10) g], but there was no difference between hyperthyroid and control groups in the wet weight of soleus [(107.3±8.6) mg vs (115.1±6.9) mg]. The time to peak tension (TPT) and time from peak tension to 75% relaxation (TR(75)) in twitch contraction were shortened in the soleus of hyperthyroid rats, and the TR(75) of tetanic contraction was also shortened as compared with that in the control group [(102.8±4.1) ms vs (178.8±15.8) ms]. The optimal stimulation frequency at which a maximal tension of tetanic contraction happened was shifted from 100 Hz in the control group to 140 Hz in hyperthyroid group. The soleus of hyperthyroid rat was easier to fatigue than that of the control rat during intermittent tetanic contraction. The SERCA activity also increased in soleus of hyperthyroid rat. The TR(75) in tetanic contraction was prolonged and showed an increased fatigue resistance in the soleus of control and hyperthyroid groups treated with 1.0 μmol/L CPA. The fatigue resistance of tetanic contraction in the soleus of hyperthyroid rat increased further with 5.0 μmol/L CPA treatment, but the resting tension kept rising. The 10 μmol/L CPA reduced the fatigue resistance of tetanic contraction in the soleus of hyperthyroid rat. The above results demonstrate that the SERCA activity in soleus can also influence the relaxation duration of twitch contraction like that in the myocardium. The SERCA activity in slow-twitch fibers is possibly involved in the regulation of fatigue resistance of intermittent tetanic contraction.