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.