Drug interaction with cardiac and skeletal muscle troponin C.

The effects of certain drugs on the binding of divalent cations to Ca(2+)-specific and Ca/Mg sites on cardiac and skeletal troponin C molecules were investigated by fluorescence and circular dichroism spectroscopy. Nicardipine and two new cardiotonic agents, APP 201-533 and DPI 201-106, interact with the N-terminal domain of troponin C, and either do not affect or, in the case of DPI 201-106, slightly increase the affinity of the Ca(2+)-specific site of troponin C for Ca2+ ion. Compound 48/80 seems to interact with the central alpha-helix of skeletal troponin C and affects the cation-binding properties of both the Ca(2+)-specific and the Ca/Mg sites of the protein. Trifluoperazine and calmidazolium (R24571) interact with the C-terminal domain of troponin C and increase the affinity of the Ca/Mg sites located there. At high concentrations these compounds interact with the N-terminal domain of troponin C and increase the affinity of the Ca(2+)-specific site. According to fluorescence spectroscopy data, R24571 induces conformational changes in troponin C similar to those evoked by troponin I. The experimental data suggest that the drugs studied act in similar ways with troponin C and calmodulin.