title: 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 (I(Ca-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 I(Ca-L) in normal and H2O2-treated neonatal rat ventricular myocytes. LPA treatment (24h) increased the action potential duration (APD) and I(Ca-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 8h, respectively. A CaN inhibitor (FK-506) prevented LPA-induced APD, I(Ca-L), and Ca(v)1.2 mRNA and protein down-regulation. The LPA-induced I(Ca-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 I(Ca-L) in normal ventricular myocytes by increasing the single-channel open probability of L-type calcium channels, and LPA decreases I(Ca-L) in H2O2-treated cardiomyocytes via the CaN-NFAT pathway.
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Renren
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, First Hospital of Jilin University, Changchun 130021, China; Department of Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Duoduo
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China. Electronic address: cyzhao@hotmail.com.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China. Electronic address: wenjie@jlu.edu.cn.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020013:Calcium Signaling; D002478:Cells, Cultured; D015870:Gene Expression; D006352:Heart Ventricles / Q000166:cytology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology*; D032342:Muscle Cells / Q000187:drug effects / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017208:Rats, Wistar
chemical_list: D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D008246:Lysophospholipids; D050778:NFATC Transcription Factors; D006861:Hydrogen Peroxide; C032881:lysophosphatidic acid
keywords: Ca(v)1.2; Calcineurin; H(2)O(2); L-type calcium current; Lysophosphatidic acid; NFAT