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

作者：Sun, Renren; Zhang, Duoduo; Zhang, Jun; Feng, Qiuyan; Zhang, Yan; Zhao, Chunyan^*; Zhang, Wenjie

来源：Prostaglandins & Other Lipid Mediators, 2015, 118: 1-10.

DOI：10.1016/j.prostaglandins.2015.03.008

• Lysophosphatidic acid
• H2O2
• L-type calcium current
• Ca(v)1.2
• Calcineurin
• NFAT

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 (24 h) 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 Ca(v)1.2 mRNA and protein expression levels at 4 and 8 h, respectively. A CaN inhibitor (FK-506) prevented LPA-induced APD, ICa-L, and Ca(v)1.2 mRNA and protein down-regulation. The LPA-induced ICa-L increase in normal cardiomyocytes was CaN-NFAT signaling-independent, and LPA did not affect Ca(v)1.2 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.

• 出版日期2015-6
• 单位吉林大学