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 Ca(2+) currents, an effect which underlies altered vascular contractility and cardiac myocyte function.


METHODS
Ca(2+) currents (I(Ca)) were recorded by whole-cell patch-clamp in HEK293 cells expressing L-type Ca(2+) channel alpha(1C) subunits or isolated rat ventricular myocytes. oxLDL (but not native LDL) significantly enhanced recombinant I(Ca), an effect mimicked by 1 microM lysophosphatidylcholine (LPC). LPC failed to enhance I(Ca) either in mitochondrial electron transport chain-depleted rho(0) cells, or in the presence of rotenone (1 microM), or MPP(+) (10 microM). The LPC response was similarly ablated by ascorbate (200 microM) or TROLOX (500 microM) and by the mitochondria-targeted antioxidant, MitoQ (250 nM). In myocytes, enhancement of I(Ca) due to LPC was similarly abrogated with rotenone and MitoQ. These data suggest that LPC enhanced recombinant Ca(2+) 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.


CONCLUSIONS
LPC up-regulates L-type Ca(2+) currents due to altered mitochondrial ROS production, an effect which mediates the response of the native I(Ca) in cardiac myocytes to oxLDL.
Fearon
Ian M
IM
Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, UK. ian.fearon@manchester.ac.uk
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002460:Cell Line; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D020746:Calcium Channels, L-Type; D045222:Electron Transport Chain Complex Proteins; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein