Different effects of lysophosphatidic acid on L-type calcium current in neonatal rat ventricular myocytes with and without H2O2 treatment

Abstract

L-type calcium current (ICa-L) alterations are implicated in various cardiac diseases, and the lysophosphatidic acid (LPA) level increases in several ischemic heart diseases. We investigated the effects of LPA on ICa-L in normal and H2O2-treated neonatal rat ventricular myocytes. LPA treatment (24h) increased the action potential duration (APD) and ICa-L in normal ventricular myocytes, but it decreased these parameters in H2O2-treated myocytes. LPA increased the single-channel open probability of L-type calcium channels in both normal and H2O2-treated myocytes. LPA activated calcineurin (CaN) and induced the cytoplasm-to-nucleus translocation of nuclear factor of activated T-cells (NFAT) in H2O2-treated cardiomyocytes. In H2O2-treated cardiomyocytes, LPA decreased Cav1.2 mRNA and protein expression levels at 4 and 8h, respectively. A CaN inhibitor (FK-506) prevented LPA-induced APD, ICa-L, and Cav1.2 mRNA and protein down-regulation. The LPA-induced ICa-L increase in normal cardiomyocytes was CaN–NFAT signaling-independent, and LPA did not affect Cav1.2 mRNA or protein expression. In conclusion, LPA increases the ICa-L in normal ventricular myocytes by increasing the single-channel open probability of L-type calcium channels, and LPA decreases ICa-L in H2O2-treated cardiomyocytes via the CaN–NFAT pathway.