Thyroid hormones
For about 30 years, it has been known that Na⁺,K⁺-ATPase activity in skeletal muscle and other tissues increases as a function of thyroid status; hyperthyroidism gives rise to an increase in pump activity, while hypothyroidism results in its decreased activity [20]. The increase in Na⁺,K⁺ transport associated with hyperthyroidism was once thought to account for the calorigenic action of the thyroid hormones, however, only 5-10% of the total heat produced in skeletal muscle of eu-, hypo- and hyperthyroid animals can be attributed to active Na⁺,K⁺ transport [7].

Na⁺,K⁺-ATPase in rat muscle
Thyroid hormones largely determine the concentration of Na⁺,K⁺ pumps in skeletal muscle through a general endocrine effect [5,7], which is in stark contrast to observations made during training (see later). In rat skeletal muscle, the Na⁺,K⁺-ATPase concentration is approximately the same whether it consists predominantly of slow (eg. soleus) or fast (eg. gastrocnemius) fibres [21]. However, gastrocnemius muscle recovered from hyperthyroid rats contained five times the concentration of Na⁺,K⁺ pumps compared to equivalent samples recovered from hypothyroid animals. This difference rose to as much as ten times when soleus muscle samples were compared. These findings suggest that muscles show a greater response to an alteration in thyroid status when they consist predominantly of slow fibres.

Fatigability and Na⁺,K⁺ pump capacity
Contrary to expectations, the soleus muscle of hyperthyroid rats shows a greater susceptibility to fatigue and less endurance [13,19] than its increased capacity for active Na⁺,K⁺-transport suggests [12,19,21]. However, when this phenomenon is considered in relation to the increased influx of Na⁺ through specialised channels, it is likely that muscle endurance is determined by the leak-to-pump ratio of Na⁺, not by the Na⁺,K⁺ pump concentration alone. Furthermore, studies in which the time course of the effects of thyroid hormone on Na⁺ influx and K⁺ efflux was compared with that on Na⁺,K⁺-ATPase activity in skeletal muscle, have shown that the rise in the unidirectional flux of cations preceded the rise in Na⁺,K⁺ pump concentration [12,19]. Thus, increased permeability of the sarcolemma to cations after thyroid hormone treatment may be the driving force for the synthesis of Na⁺,K⁺ pumps.

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