Calcium-independent phospholipase A2 mediates store-operated calcium entry in rat cerebellar granule cells

Abstract

Store-operated Ca(2+) entry (SOCE) has been extensively studied in non-neuronal cells, such as glial cells and smooth muscle cells, in which Ca(2+)-independent phospholipase A(2) (iPLA(2)) has been shown to play a key role in the regulation of SOCE channels. In the present study, we have investigated the role of iPLA(2) for store-operated Ca(2+) entry in rat cerebellar granule neurons in acute brain slices using confocal Ca(2+) imaging. Depletion of Ca(2+) stores by cyclopiazonic acid (CPA) induced a Ca(2+) influx, which could be inhibited by SOCE channel blockers 2-aminoethoxy-diphenylborate (2-APB) and 3,5-bistrifluoromethyl pyrazole derivative (BTP2), but not by the voltage-operated Ca(2+) channel blocker diltiazem and by the Na+ channel blocker tetrodotoxin. The inhibitors of iPLA(2), bromoenol lactone (BEL) and 1,1,1-trifluoro-2-heptadecanone, and the selective suppression of iPLA(2) expression by antisense oligodeoxynucleotides, inhibited CPA-induced Ca(2+) influx. Calmidazolium, which relieves the block of inhibitory calmodulin from iPLA(2), elicited a Ca(2+) influx similar to CPA-induced Ca(2+) entry. The product of iPLA(2), lysophosphatidylinositol, elicited a 2-APB- and BTP2-sensitive, but BEL-insensitive, Ca(2+) influx. Spontaneous Ca(2+) oscillations in granule cells in acute brain slices were reduced after inhibiting iPLA(2) activity or by blocking SOCE channels. The results suggest that depletion of Ca(2+) stores activates iPLA(2) to trigger Ca(2+) influx by the formation of lysophospholipids in these neurons.

Effect of Methoxychlor on Ca2+ Handling and Viability in OC2 Human Oral Cancer Cells

“…Singaravelu et al. [34] showed that phospholipase A2 mediates Ca 2+ influx in rat cerebellar granule cells.…”

Effect of thimerosal on Ca2+ movement and apoptosis in PC3 prostate cancer cells

“…Notably, recent evidence shows that PLA2 controls endothelial store‐operated Ca 2+ entry and vascular tone in intact aorta [Boittin et al, 2008], and enhances store‐operated Ca 2+ entry in dystrophic skeletal muscle fibers [Boittin et al, 2006]. Singaravelu et al [2008] showed that phospholipase A2 mediated store‐operated Ca 2+ entry in rat cerebellar granule cells. Thus, the present studies are consistent with data that phospholipase A2 activity was required for thimerosal‐evoked Ca 2+ signal in PC3 cells.…”

Maprotiline‐induced Ca2+ fluxes and apoptosis in human osteosarcoma cells

“…Lupescu et al [2006] reported that human parvovirus B19 capsid protein VP1-evoked Ca 21 influx was inhibited if phospholipase A2 activity was suppressed. Evidence also shows that PLA2 regulates endothelial entry and vascular tone in intact aorta [Boittin et al, 2008], and stimulates store-operated Ca 21 entry in dystrophic skeletal muscle fibers [Boittin et al, 2006] and rat cerebellar granule cells [Singaravelu et al, 2008]. Another possible mechanism that might contribute to maprotiline-induced [ Lin et al, 2009;Lu et al, 2009].…”