Effects of methyl methacrylate on Ca 2+ uptake of cardiac sarcoplasmic reticulum

Abstract

In isolated cardiac sarcoplasmic reticulum (SR) vesicles, methyl methacrylate (2.5–100 mM) directly inhibited initial rates of Ca 2+ uptake as well as the maximal uptake. Inhibition of SR Ca 2+ uptake by methyl methacrylate was concentration-dependent, and the highest concentration of methyl methacrylate (100 mM) almost completely inhibited the SR Ca 2+ uptake. EC 50 of methyl methacrylate in percent inhibition of SR Ca 2+ uptake was 16.1, 31.9, and 53.4 mM at pCa 7.0, 6.6, and 6.0, respectively. At low Ca 2+ concentrations (0.1–1 μM), SR vesicles treated with 20 mM methyl methacrylate showed the decreased Ca 2+ uptake rates. However, further increase of Ca 2+ concentration to pCa 5.5 abolished the inhibitory effect of methyl methacrylate on SR Ca 2+ uptake, showing no difference between the control and the methyl methacrylate-treated SR vesicles. From these results we could conclude that methyl methacrylate exerts a direct inhibition of cardiac SR Ca 2+ uptake. This mechanism, at least in part, might contribute to the profound hypotension induced by methyl methacrylate. Supplementation of calcium ion appears to reduce the methyl methacrylate-induced cardiovascular disturbances efficiently.