Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA

Voltage-activated Ca2+ channels (VACCs) mediate Ca2+ influx to trigger action potential-evoked neurotransmitter release, but the mechanism by which Ca2+ regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type.