Differential effects of Ca2+ channel blockers on Ca2+ overload induced by lysophosphatidylcholine in cardiomyocytes

The effects of Ca2+ channel blockers (verapamil, diltiazem, nicardipine, bepridil and flunarizine) on Ca2+ overload induced by lysophosphatidylcholine were examined in rat isolated cardiomyocytes. Addition of lysophosphatidylcholine (15 microM) produced Ca2+ overload as evidenced by a marked increase in the concentration of intracellular Ca2+ and hypercontracture of cells. Verapamil, flunarizine and bepridil concentration dependently inhibited the lysophosphatidylcholine-induced Ca2+ overload, whereas diltiazem and nicardipine did not. Lysophosphatidylcholine increased the release of creatine kinase, which was significantly attenuated by verapamil, flunarizine or bepridil (5 microM for each), but not by diltiazem or nicardipine (20 microM for each). Verapamil, flunarizine, bepridil (which attenuated the lysophosphatidylcholine-induced Ca2+ overload) and nicardipine (which did not) inhibited the veratridine-induced increase in the concentration of intracellular Na+ (indicated by the increase in fluorescence ratio of Na(+)-binding benzofuran isophthalate) and cell contracture, whereas diltiazem did not. These results suggest that verapamil, bepridil and flunarizine attenuate the Ca2+ overload induced by lysophosphatidylcholine, and that the Ca2+ channel blocking action of these drugs does not contribute substantially to this effect. The Na+ channel inhibition together with high lipophilicity of these drugs may be important for the attenuation of the lysophosphatidylcholine-induced Ca2+ overload.