TABLE 2

Effects of TFP and anthracyclines on SR Ca2+ release

In control experiments, canine cardiac sarcoplasmic reticulum vesicles (0.34 mg of protein/ml) in 0.30 mM antipyrylazo III, 20 mM MOPS, pH 7.0, 50 mM KH2PO4, 5 mM KCl, 2 mM MgCl2, and 2 mM ATP were loaded with Ca2+ (7 nmol/load). In drug experiments, TFP or anthracycline was added to the microsomes before Ca2+ loading or after the sixth or seventh load. In both drug and control experiments, Ca2+ efflux rates (nanomoles of Ca2+ per minute per milligram) as a result of the addition of 6 mM caffeine were determined spectrophotometrically. A total of 10 Ca2+ loads were used in the TFP experiments; 11 loads were used in the anthracycline experiments. Concentrations of drug used in Ca2+ load dependence studies were 50 μM TFP and 1 μM daunorubicin and daunorubicinol.

Ca2+ Load Dependence
Drug Dose Dependence IC50 Load at Which Drug Was Added Observed Release Rate
μM % of control
TFP 40 0 40
7 68
Daunorubicina 1.2 0 56
6 68
Daunorubicinola 0.6 0 43
6 62
  • a Data from Olson et al. (2000).