Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients

The cellular mechanisms responsible for large miniature currents in some br ain synapses remain undefined. In Purkinje cells, we found that large-ampli tude miniature inhibitory postsynaptic currents (mIPSCs) were inhibited by ryanodine or by long-term removal of extracellular Ca2+. Two-photon Ca2+ im aging revealed random, ryanodine-sensitive intracellular Ca2+ transients, s patially constrained at putative presynaptic terminals. At high concentrati on, ryanodine decreased action-potential-evoked rises in intracellular Ca2. Immuno-localization showed ryanodine receptors in these terminals. Our da ta suggest that large mIPSCs are multivesicular events regulated by Ca2+ re lease from ryanodine-sensitive presynaptic Ca2+ stores.