Influence of thyroid hormone on some electrophysiological properties of developing rat skeletal muscle cells in culture.

Effects of thyroxine (T4) were examined on some electrophysiological properties of developing rat myotubes in culture. Thyroxine caused an increase in transmembrane resting potential (Em) of skeletal myotubes. Ouabain decreases Em in both control and T4-treated cells within 5-15 min of addition to the culture. Moreover, the effect of T4 is nearly eliminated by short-term ouabain treatment and by reduced extracellular K+ concentration. The change in Em in response to a 10-fold increase in extracellular K+ concentration is not altered by T4-treatment despite the higher Em of T4-treated cells. Studies on developmental effects of T4 showed that Em of T4-treated cells is higher than controls by as early as day 5. By this time, ouabain decreases Em of T4-treated cells but not that of untreated controls. Treatment with T4 also causes an increase in frequency of spontaneously-occurring action potentials generated by cultured myotubes. Chronic treatment with tetrodotoxin blocks this effect without affecting the T4-induced increase in Em. The findings demonstrate that activity of electrogenic Na,K-ATPase is increased by T4-treatment and that this effect is primarily responsible for the elevated Em in T4-treated cells. In addition, it appears that T4 causes the activity of this enzyme to be manifest earlier in development than might otherwise occur in cultured muscle. Finally, stimulation of electrogenic pump activity is not secondary to increased influx of Na+ ions associated with increased electrical activity and probably results from synthesis of new enzyme units in both developing and mature myotubes.