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

The distance between Ca(V)2.1 voltage-gated Ca2+ channels and the Ca2+ 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 CaV2.1 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.

Automated summary

Using superresolution structured illumination microscopy, we investigated the nanoscale organization of two Ca(V)2.1 splice isoforms at presynaptic terminals. We found that Ca(V)2.1[EFa] is more tightly co-localized with presynaptic markers, indicating that alternative splicing plays a crucial role in the synaptic organization of Ca(V)2.1 channels.