AUTHOR=Eguchi Kohgaku , Montanaro Jacqueline , Le Monnier Elodie , Shigemoto Ryuichi TITLE=The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals JOURNAL=Frontiers in Neuroanatomy VOLUME=Volume 16 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2022.846615 DOI=10.3389/fnana.2022.846615 ISSN=1662-5129 ABSTRACT=Upon the arrival of action potentials at nerve terminals, neurotransmitters are released from synaptic vesicles (SVs) by exocytosis. CaV2.1, 2.2, and 2.3 are the major subunits of the voltage-gated calcium channel (VGCC) responsible for increasing intra-terminal calcium levels and triggering SV exocytosis in the CNS synapses. Two-dimensional analysis of CaV2 distributions using SDS-digested freeze-fracture replica labeling (SDS-FRL) has revealed their numbers, densities, and nanoscale clustering patterns in individual presynaptic active zones. The variation in these properties affects the coupling of VGCCs with calcium sensors on SVs, synaptic efficacy, and temporal precision of transmission. Here we summarize how the morphological parameters of CaV2 distribution obtained by SDS-FRL differ depending on different types of synapses and could correspond to functional properties in synaptic transmission.