Inactivation of excitation-contraction coupling was examined in extensor digitorum longus (EDL) and soleus muscle fibers from rats injected daily with tri-iodothyronine (T3, 150 micrograms/kg) for 10-14 d. Steady-state activation and inactivation curves for contraction were obtained from measurements of peak potassium contracture tension at different surface membrane potentials. The experiments tested the hypothesis that noninactivating tension is a "window" tension caused by the overlap of the activation and inactivation curves. Changes in the amplitude and voltage dependence of noninactivating tension should be predicted by the changes in the activation and inactivation curves, if noninactivating tension arises from their overlap. After T3 treatment, the area of overlap increased in EDL fibers and decreased in soleus fibers and the overlap region was shifted to more negative potentials in both muscles. Noninactivating tension also appeared at more negative membrane potentials after T3 treatment in both EDL and soleus fibers. The effects of T3 treatment were confirmed with a two microelectrode voltage-clamp technique: at the resting membrane potential (-80 mV) contraction in response to a brief test pulse required less than normal depolarization in EDL, but more than normal depolarization in soleus fibers. After T3 treatment, the increase in contraction threshold at depolarized holding potentials (attributed to inactivation) occurred at more depolarized holding potentials in EDL, or less depolarized holding potentials in soleus. The changes in contraction threshold could be accounted for by the effects of T3 on the activation and inactivation curves. In conclusion, (a) T3 appeared to affect the expression of both activation and inactivation characteristics, but the activation effects could not be cleanly distinguished from T3 effects on the sarcoplasmic reticulum and contractile proteins, and (b) the experiments provided evidence for the hypothesis that the noninactivating tension is a steady-state "window" tension.

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