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

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Abstract

Store-operated Ca2+ entry (SOCE) has been extensively studied in non-neuronal cells, such as glial cells and smooth muscle cells, in which Ca2+-independent phospholipase A2 (iPLA2) has been shown to play a key role in the regulation of SOCE channels. In the present study, we have investigated the role of iPLA2 for store-operated Ca2+ entry in rat cerebellar granule neurons in acute brain slices using confocal Ca2+ imaging. Depletion of Ca2+ stores by cyclopiazonic acid (CPA) induced a Ca2+ 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 Ca2+ channel blocker diltiazem and by the Na+ channel blocker tetrodotoxin. The inhibitors of iPLA2, bromoenol lactone (BEL) and 1,1,1-trifluoro-2-heptadecanone, and the selective suppression of iPLA2 expression by antisense oligodeoxynucleotides, inhibited CPA-induced Ca2+ influx. Calmidazolium, which relieves the block of inhibitory calmodulin from iPLA2, elicited a Ca2+ influx similar to CPA-induced Ca2+ entry. The product of iPLA2, lysophosphatidylinositol, elicited a 2-APB- and BTP2-sensitive, but BEL-insensitive, Ca2+ influx. Spontaneous Ca2+ oscillations in granule cells in acute brain slices were reduced after inhibiting iPLA2 activity or by blocking SOCE channels. The results suggest that depletion of Ca2+ stores activates iPLA2 to trigger Ca2+ influx by the formation of lysophospholipids in these neurons.

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  1. Abteilung für Allgemeine Zoologie, FB Biologie, TU Kaiserslautern, Postfach 3049, D-67653, Kaiserslautern, Germany

    Karthika Singaravelu, Christian Lohr & Joachim W. Deitmer

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  1. Karthika Singaravelu
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  2. Christian Lohr
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Correspondence to Joachim W. Deitmer.

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Singaravelu, K., Lohr, C. & Deitmer, J.W. Calcium-independent phospholipase A2 mediates store-operated calcium entry in rat cerebellar granule cells. Cerebellum 7, 467–481 (2008). https://doi.org/10.1007/s12311-008-0050-z

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