Effects of methyl methacrylate on Ca2+ uptake of cardiac sarcoplasmic reticulum.
In isolated cardiac sarcoplasmic reticulum (SR) vesicles, methyl methacrylate (2.5-100mM) directly inhibited initial rates of Ca2+ uptake as well as the maximal uptake. Inhibition of SR Ca2+ uptake by methyl methacrylate was concentration-dependent, and the highest concentration of methyl methacrylate (100mM) almost completely inhibited the SR Ca2+ uptake. EC(50) of methyl methacrylate in percent inhibition of SR Ca2+ uptake was 16.1, 31.9, and 53.4mM at pCa 7.0, 6.6, and 6.0, respectively. At low Ca2+ concentrations (0.1-1 microM), SR vesicles treated with 20mM methyl methacrylate showed the decreased Ca2+ uptake rates. However, further increase of Ca2+ concentration to pCa 5.5 abolished the inhibitory effect of methyl methacrylate on SR Ca2+ 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 Ca2+ 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.
Kim
Young-Hoon
YH
Department of Pharmacology, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
Cho
Yong Sun
YS
Kim
Hae Won
HW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D020366:Methylmethacrylate / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism*
D020366:Methylmethacrylate; D002118:Calcium