TY - JOUR
T1 - Calcium‐Dependent and ‐Independent Acetylcholine Release from Electric Organ Synaptosomes by Pardaxin
T2 - Evidence of a Biphasic Action of an Excitatory Neurotoxin
AU - Arribas, Mònica
AU - Blasi, Joan
AU - Lazarovici, Philip
AU - Marsal, Jordi
PY - 1993/2
Y1 - 1993/2
N2 - Abstract: The effect of pardaxin, a new excitatory neurotoxin, on neurotransmitter release was tested using purely cholinergic synaptosomes of Torpedo marmorata electric organ. Pardaxin elicited the release of acetylcholine with a biphasic dose dependency. At low concentrations (up to 3 × 10−7M), the release was calcium‐dependent and synaptosomal structure was well preserved as revealed by electron microscopy and measurements of occluded lactate dehydrogenase activity. At concentrations from 3 × 10−7M to 10−5M, the pardaxin‐induced release of acetylcholine was independent of extracellular calcium, and occluded synaptosomal lactate dehydrogenase activity was lowered, indicating a synaptosomal membrane perturbation. Electron microscopy of 10−6M pardaxin‐treated synaptosomes revealed nerve terminals depleted of synaptic vesicles and containing cisternae. At higher toxin concentrations ( 10−5M), there were striking effects on synaptosomal morphology and occluded lactate dehydrogenase activity, suggesting a membrane lytic effect. We conclude that, at low concentrations, this neurotoxin is a promising tool to investigate calcium‐dependent mechanisms of neurotransmitter release in the nervous system.
AB - Abstract: The effect of pardaxin, a new excitatory neurotoxin, on neurotransmitter release was tested using purely cholinergic synaptosomes of Torpedo marmorata electric organ. Pardaxin elicited the release of acetylcholine with a biphasic dose dependency. At low concentrations (up to 3 × 10−7M), the release was calcium‐dependent and synaptosomal structure was well preserved as revealed by electron microscopy and measurements of occluded lactate dehydrogenase activity. At concentrations from 3 × 10−7M to 10−5M, the pardaxin‐induced release of acetylcholine was independent of extracellular calcium, and occluded synaptosomal lactate dehydrogenase activity was lowered, indicating a synaptosomal membrane perturbation. Electron microscopy of 10−6M pardaxin‐treated synaptosomes revealed nerve terminals depleted of synaptic vesicles and containing cisternae. At higher toxin concentrations ( 10−5M), there were striking effects on synaptosomal morphology and occluded lactate dehydrogenase activity, suggesting a membrane lytic effect. We conclude that, at low concentrations, this neurotoxin is a promising tool to investigate calcium‐dependent mechanisms of neurotransmitter release in the nervous system.
KW - Acetylcholine release
KW - Cholinergic synaptosomes
KW - Excitatory neurotoxin
KW - Pardaxin
KW - Pore‐forming
UR - http://www.scopus.com/inward/record.url?scp=0027465996&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.1993.tb03184.x
DO - 10.1111/j.1471-4159.1993.tb03184.x
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C2 - 8419536
AN - SCOPUS:0027465996
SN - 0022-3042
VL - 60
SP - 552
EP - 558
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -