OxLDL enhances L-type Ca2+ currents via lysophosphatidylcholine- induced mitochondrial reactive oxygen species (ROS) production

Objective: To examine the mechanisms underlying oxidised LDL- (oxLDL)-induced alterations in Ca2+ currents, an effect which underlies altered vascular contractility and cardiac myocyte function. Methods: Ca2+ currents (ICa) were recorded by whole-cell patch-clamp in HEK293 cells expressing L-type Ca2+ channel α1C subunits or isolated rat ventricular myocytes. oxLDL (but not native LDL) significantly enhanced recombinant ICa, an effect mimicked by 1 μM lysophosphatidylcholine (LPC). LPC failed to enhance I Ca either in mitochondrial electron transport chain-depleted ρ0 cells, or in the presence of rotenone (1 μM), or MPP + (10 μM). The LPC response was similarly ablated by ascorbate (200 μM) or TROLOX (500 μM) and by the mitochondria-targeted antioxidant, MitoQ (250 nM). In myocytes, enhancement of ICa due to LPC was similarly abrogated with rotenone and MitoQ. These data suggest that LPC enhanced recombinant Ca2+ currents due to increased mitochondrial ROS production. In support with this, LPC enhanced fluorescence in HEK293 cells and cardiac myocytes loaded with a ROS-sensitive mitochondrial dye, reduced mitotracker red. Conclusion: LPC up-regulates L-type Ca2+ currents due to altered mitochondrial ROS production, an effect which mediates the response of the native ICa in cardiac myocytes to oxLDL. © 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.