Differential effects of Ca 2+ channel blockers on Ca 2+ 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 μM) 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 μM for each), but not by diltiazem or nicardipine (20 μM 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.