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The distance between Ca V 2.1 voltage-gated Ca 2+  channels and the Ca 2+  sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of Ca V 2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two Ca V 2.1 splice isoforms (Ca V 2.1[EFa] and Ca V 2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that Ca V 2.1[EFa] is more tightly co-localized with presynaptic markers than Ca V 2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of Ca V 2.1 channels.

Nanoscale organization of Ca V 2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation