Figure 7. Model of different mechanisms of depolarization-induced neuropeptide secretion from OT/VP axon terminals.

1) Normally, secretion is activated by Ca²⁺ entry via different types of voltage-gated Ca²⁺ channels (VGCC). 2) Independent of extracellular Ca²⁺, ryanodine type-1 receptors are activated in response to depolarization while mechanically tethered to nifedipine-sensitive Ca²⁺ channels. Depolarization, thus, allows for release of Ca²⁺ from ryanodine-sensitive stores contributing to the overall increase in intraterminal [Ca²⁺]. 3) This and Ca²⁺ entry through VGCCs likely contribute to CICR from ryanodine type-2 receptors. Intra-terminal free Ca²⁺ rise triggers the exocytosis releasing OT and arginine vasopressin (AVP). 4) Finally, there is secretion directly coupled to voltage and independent of both external and internal Ca²⁺. Drawing courtesy of Drs. Cristina Velazquez & Hector Marrero.