Calcium-independent phospholipase A2 mediates store-operated calcium entry in rat cerebellar granule cells.
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.
Singaravelu
Karthika
K
Abteilung für Allgemeine Zoologie, FB Biologie, TU Kaiserslautern, Germany.
Lohr
Christian
C
Deitmer
Joachim W
JW
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D007700:Kinetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D054467:Phospholipases A2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology
D004791:Enzyme Inhibitors; D007093:Imidazoles; D016376:Oligonucleotides, Antisense; D002110:Caffeine; C031938:calmidazolium; D054467:Phospholipases A2; D011188:Potassium; D002118:Calcium
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