2,3-Butanedione 2-monoxime (BDM) induces calcium release from canine cardiac sarcoplasmic reticulum

Abstract

2,3-Butanedione 2-monoxime (BDM) is a well known inhibitor of skeletal and cardiac muscle contraction. Recently, it has been discovered that BDM has an influence on the sarcoplasmic reticulum (SR). We investigated the effects of BDM on the SR in our digitonin lysed myocyte system, which measures accumulated SR Ca2+. While BDM (30 mM) had no effect on SR Ca2+ uptake (under conditions that included Ca2+ release channel efflux inhibitors), it induced SR Ca2+ release (no efflux inhibitors) with a maximal reduction of 72% of SR Ca2+ at pCa 6.0. A titration showed that even 5 mM BDM resulted in a 45% reduction at that same pCa. Also, a positive correlation was found between the degree of BDM induced Ca2+ release and free Ca2+ concentration. Thus, the use of even low concentrations of BDM as an excitation-contraction uncoupler must be approached with caution.