Dynasore, an inhibitor of dynamin, increases the probability of transmitter release.
Dynasore was recently developed as a small molecule, selective non-competitive inhibitor of the protein dynamin. This inhibitor has been shown to block dynamin-dependent endocytosis and is now used commonly to study vesicular recycling at synapses. We have measured the effects of dynasore on spontaneous and evoked transmitter release at the frog neuromuscular junction and shown that, in addition to inhibiting endocytosis, dynasore increases the probability of transmitter release. Furthermore, we have shown that dynasore exposure leads to an increase in resting intra-terminal calcium, but this effect does not completely account for the dynasore-mediated increase in the probability of transmitter release. Therefore, in interpreting effects of the dynamin inhibitor dynasore at synapses, one must be alert to potential increases in presynaptic calcium concentration and transmitter release probability.
Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260, USA.
H L
HL
Douthitt
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Luo
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McCann
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Meriney
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D034281:Dynamins / Q000037:antagonists & inhibitors* / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D006835:Hydrazones / Q000494:pharmacology*; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D015233:Models, Statistical; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism*; D011894:Rana pipiens; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology
D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D034281:Dynamins; D000109:Acetylcholine; D002118:Calcium