Thyroid hormone-induced upregulation of Na channels and Na-K pumps: implications for contractility

We have previously observed in rat soleus muscle that endurance is a function of the ratio between the concentration of Na+ channels and Na(+)-K+ pumps [Harrison, A. P., O. B. Nielsen, and T. Clausen. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol. 41): R1402-R1408, 1997]. In this study we explore this relationship further by comparing the changes in Na+ channel and Na(+)-K+ pump concentrations induced by injections of 3,5,3'-triiodothyronine (T3) with endurance. T3 induced upregulation of the concentration of Na+ channels and Na(+)-K+ pumps, which was associated with a progressive loss of contractile endurance. The increase in Na+ channels preceded that of the Na(+)-K+ pumps and amounted to 49 and 52% (both P < 0.01) after 48 and 72 h of T3 treatment, respectively. Concomitantly, during 90-Hz stimulation, the initial rate of force decline increased by 42 and 45% after 48 and 72 h of T3 treatment, respectively (both P < 0.001). These observations are important for an understanding of the fatigue associated with hyperthyroidism and add further support to the hypothesis that muscle endurance depends on the leak-to-pump ratio for Na+.