Synaptotagmin I synchronizes transmitter release in mouse hippocampal neurons.
We have asked whether loss of the Ca2+ sensor protein synaptotagmin I influences the total amount of neurotransmitter released after a presynaptic action potential. Hippocampal neurons from synaptotagmin I knock-out mice had a greatly reduced fast synchronous component of glutamate release, as reported previously. However, the amount of glutamate released during the slow asynchronous component increased in these knock-out neurons. As a result of these changes in the kinetics of release, there was no significant difference between wild-type and knock-out neurons in the total amount of transmitter released within 400 msec after a presynaptic stimulus. Fluorescence imaging experiments demonstrated that wild-type and knock-out neurons take up and release similar amounts of FM dye after depolarization, indicating normal amounts of synaptic vesicle trafficking in the knock-out neurons. These results indicate that synaptotagmin I knock-out neurons are fully capable of releasing neurotransmitter, with the increased slow component of release serving to compensate for loss of the fast component. Thus, synaptotagmin I synchronizes the rapid release of neurotransmitters after Ca2+ entry into presynaptic terminals and also appears to suppress the slower, asynchronous form of transmitter release.
Nishiki
Tei-ichi
T
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Augustine
George J
GJ
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000502:physiology*; D050863:Synaptotagmin I; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D005456:Fluorescent Dyes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D050857:Synaptotagmins