1. Nanoscale Distribution of Presynaptic Ca2+ Channels and Its Impact on Vesicular Release during Development.
- Author
-
Nakamura, Yukihiro, Harada, Harumi, Kamasawa, Naomi, Matsui, Ko, Rothman, Jason S., Shigemoto, Ryuichi, Silver, R. Angus, DiGregorio, David A., and Takahashi, Tomoyuki
- Subjects
- *
SYNAPSES , *CALCIUM channels , *VOLTAGE-gated ion channels , *IMMUNOGOLD labeling , *ETHYLENE glycol , *ACETIC acid , *BUFFER solutions - Abstract
Summary Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca 2+ 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 Ca v 2.1 channels, local [Ca 2+ ] 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 Ca 2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca 2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30 nm) 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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF