Calcium dependence of spontaneous neurotransmitter release

Spontaneous release of neurotransmitters is regulated by extracellular [Ca2+] and intracellular [Ca2+]. Curiously, some of the mechanisms of Ca2+ signaling at central synapses are different at excitatory and inhibitory synapses. While the stochastic activity of voltage-activated Ca2+ channels triggers a majority of spontaneous release at inhibitory synapses, this is not the case at excitatory nerve terminals. Ca2+ release from intracellular stores regulates spontaneous release at excitatory and inhibitory terminals, as do agonists of the Ca2+-sensing receptor. Molecular machinery triggering spontaneous vesicle fusion may differ from that underlying evoked release and may be one of the sources of heterogeneity in release mechanisms.