Inhibition of Ca²⁺ accumulation in isolated sarcoplasmic reticulum by thyroid hormones

Thyroid hormones inhibit Ca²⁺ accumulation and ATPase activity of isolated sarcoplasmic reticulum vesicles. Half-maximal inhibition was obtained by about 2.5 μM. The ATP hydrolysis activity of the purified (Ca²⁺ + Mg²⁺)-ATPase or the SR vesicles, in the presence of the Ca²⁺ ionophore A23187, is not inhibited by T₃ or T₄. Modification of T₃ or T₄ in the ring portion, but not in the amino portion, of te molecules results in T₄ and T₃ analogues which are unable to inhibit Ca²⁺ accumulation. T₃ and T₄ have no significant effect on various partial reactions of the transport cycle such as: the binding of ATP and Ca²⁺, or ADP-ATP exchange and E-P formation from ATP, but they inhibit the E-P formation from inorganic phosphate (P_i) and ATP-P_i exchange. The inhibition of both Ca²⁺ accumulation and ATPaseactivity by T₃ or T₄ is increased in the presence of P_i. Binding sites for [¹²⁵I]T₃ and for [¹²⁵I]T₄ in SR proteins were demonstrated using either equilibrium dialysis or gel overlay techniques. The results suggest that the thyroid hormones inhibit the ATP-dependent Ca²⁺ accumulation, probably by inhibiting the transport of anions which act as the Ca²⁺ precipitating anion.