Nanoscale Distribution of Presynaptic Ca2+ Channels and Its Impact on Vesicular Release during Development

Yukihiro Nakamura, Harumi Harada, Naomi Kamasawa, Ko Matsui, Jason S. Rothman, Ryuichi Shigemoto, R. Angus Silver, David A. DiGregorio, Tomoyuki Takahashi

    Research output: Contribution to journalArticlepeer-review

    134 Citations (Scopus)


    Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.

    Original languageEnglish
    Pages (from-to)145-158
    Number of pages14
    Issue number1
    Publication statusPublished - 2015 Jan 7

    ASJC Scopus subject areas

    • Neuroscience(all)


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