Chemical neurotransmission is the major form of communication between neurons and is essential for CNS function. Glutamate is an excitatory fast-acting neurotransmitter that mediates inter-neuronal communication. Evoked and spontaneous release of neurotransmitters are proposed to have distinct roles and rely on divergent vesicle pools and receptors. Moreover, changes in extracellular [Ca2+] ([Ca2+]o) are shown to differentially affect the probability of release for each mechanism. Ca2+ entry via voltage-gated calcium channels (VGCCs) is responsible for evoked release however the same pathway does not contribute to spontaneous release. How does extracellular [Ca2+]o stimulate spontaneous release?