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Significance Synaptic vesicle (SV) release from presynaptic terminals requires nanometer precise control of action potential (AP)–triggered calcium influx through voltage-gated calcium channels (VGCCs). SV recycling also depends on calcium signals, though in different spatiotemporal domains. Mechanisms for separate control of SV release and recycling by AP-triggered calcium influx remain elusive. Here, we demonstrate largely independent regulation of release and recycling by two different populations of VGCCs (Cav 2, Cav 1), identify Cav 1 as one of potentially multiple calcium entry routes for endocytosis regulation, and show functional separation of simultaneous calcium signals in the nanometer space of a presynaptic terminal by the plasma membrane calcium ATPase (PMCA). The Cav 2/Cav 1/PMCA functional triad may provide conserved means for independent control of different vital presynaptic functions.

proceedings of the national academy of sciences of the united states of america

Separation of presynaptic Ca v 2 and Ca v 1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca 2+ pump PMCA