Calcium influx and mitochondrial alterations at synapses exposed to snake neurotoxins or their phospholipid hydrolysis products.
Snake presynaptic phospholipase A2 neurotoxins (SPANs) bind to the presynaptic membrane and hydrolyze phosphatidylcholine with generation of lysophosphatidylcholine (LysoPC) and fatty acid (FA). The LysoPC+FA mixture promotes membrane fusion, inducing the exocytosis of the ready-to-release synaptic vesicles. However, also the reserve pool of synaptic vesicles disappears from nerve terminals intoxicated with SPAN or LysoPC+FA. Here, we show that LysoPC+FA and SPANs cause a large influx of extracellular calcium into swollen nerve terminals, which accounts for the extensive synaptic vesicle release. This is paralleled by the change of morphology and the collapse of membrane potential of mitochondria within nerve bulges. These results complete the picture of events occurring at nerve terminals intoxicated by SPANs and define the LysoPC+FA lipid mixture as a novel and effective agonist of synaptic vesicle release.
Rigoni
Michela
M
Department of Biomedical Sciences and Consiglio Nazionale Ricerche Institute of Neuroscience, University of Padova, 35121 Padova, Italy.
Pizzo
Paola
P
Schiavo
Giampietro
G
Weston
Anne E
AE
Zatti
Giancarlo
G
Caccin
Paola
P
Rossetto
Ornella
O
Pozzan
Tullio
T
Montecucco
Cesare
C
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006868:Hydrolysis; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012911:Snakes; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*
D005227:Fatty Acids; D008244:Lysophosphatidylcholines; D009498:Neurotoxins; D010743:Phospholipids; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium