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

Abstract The effects of Ca 2+ channel blockers (verapamil, diltiazem, nicardipine, bepridil and flunarizine) on Ca 2+ overload induced by lysophosphatidylcholine were examined in rat isolated cardiomyocytes. Addition of lysophosphatidylcholine (15 μ M) produced Ca 2+ overload as evidenced by a marked increase in the concentration of intracellular Ca 2+ and hypercontracture of cells. Verapamil, flunarizine and bepridil concentration dependently inhibited the lysophosphatidylcholine-induced Ca 2+ overload, whereas diltiazem and nicardipine did not. Lysophosphatidylcholine increased the release of creatine kinase, which was significantly attenuated by verapamil, flunarizine or bepridil (5 μ M for each), but not by diltiazem or nicardipine (20 μ M for each). Verapamil, flunarizine, bepridil (which attenuated the lysophosphatidylcholine-induced Ca 2+ 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 Ca 2+ overload induced by lysophosphatidylcholine, and that the Ca 2+ 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 Ca 2+ overload.