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bioRxiv · 10.1101/2020.11.10.376111

Voltage-gated calcium channels trigger spontaneous glutamate release via nanodomain coupling

Lee, B. J.·Yang, C. H.·Lee, S. Y.·Lee, S.-H.·Kim, Y.·Ho, W.-K.
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Abstract

Neurotransmitter release occurs either synchronously with action potentials (evoked release) or spontaneously (spontaneous release). Whether the molecular mechanisms underlying evoked and spontaneous release are identical, especially whether voltage-gated Ca2+ channels (VGCCs) can trigger spontaneous events, is still a matter of debate in glutamatergic synapses. To elucidate this issue, we characterized the VGCC dependence of miniature excitatory postsynaptic currents (mEPSCs) in various synapses with different coupling distances between VGCCs and synaptic vesicles, known as a critical factor in evoked release. We found that most of the extracellular calcium-dependent mEPSCs were attributable to VGCCs in cultured autaptic hippocampal neurons and the mature calyx of Held where VGCCs and vesicles were tightly coupled. Among loosely coupled synapses, mEPSCs were not VGCC-dependent at immature calyx of Held and CA1 pyramidal neuron synapses, whereas VGCCs contribution was significant at CA3 pyramidal neuron synapses. Interestingly, the contribution of VGCCs to spontaneous glutamate release in CA3 pyramidal neurons was abolished by a calmodulin antagonist, calmidazolium. These data suggest that coupling distance between VGCCs and vesicles determines VGCC dependence of spontaneous release at tightly coupled synapses, yet VGCC contribution can be achieved indirectly at loosely coupled synapses. HighlightsO_LIExtracellular Ca2+ -dependent spontaneous glutamate release is mediated by VGCCs. C_LIO_LICa2+ cooperativity of spontaneous and evoked release is comparable. C_LIO_LISynapses at different areas and ages show distinct VGCC dependence on mini events. C_LIO_LINanodomain coupling between VGCCs and Ca2+ sensors determines VGCC dependence. C_LI

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Lee, B. J., Yang, C. H., Lee, S. Y., Lee, S.-H., Kim, Y., Ho, W.-K.. 2020-11-10. Voltage-gated calcium channels trigger spontaneous glutamate release via nanodomain coupling. https://doi.org/10.1101/2020.11.10.376111

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