抄録
Neurotransmitters are released from presynaptic nerve terminals in two different ways, stimulus-evoked release and spontaneous release. It has been shown that a synaptic vesicle protein, synaptotagmin (syt) 1 serves as a Ca2+ sensor and synchronizes evoked transmitter release with a presynaptic action potential. However, a role of this protein for Ca2+-regulated spontaneous transmitter release remains uncertain. To address this question, we have studied spontaneous release from syt 1-deficient hippocampal neurons cultured on microislands. There were no significant differences in spontaneous release between wild-type and syt 1-deficient neurons, although the synchronous evoked release was abolished in syt 1 null neurons, consisting with previous results (Cell 79: 717). However, when null neurons were transfected with syt 1 harboring a mutation in either Asp309 or Asp363 in its Ca2+-binding domain, the frequency of spontaneous release was greatly reduced, but not its quantal size. Decreased frequency in spontaneous release is not due to less synapses in neurons transfected with syt 1 mutants, because the number of synapses were similar in both of wild-type neurons and those expressing mutants. These results indicate that spontaneous synaptic vesicle fusion at resting status are apparently regulated by Ca2+ binding to Asp309 and Asp363 of syt 1. Thus, syt 1 plays an important role in Ca2+-regulated spontaneous neurotransmitter release as well as evoked transmitter release. Supported by KAKENHI (18800027) [J Physiol Sci. 2008;58 Suppl:S123]
