Calcium control of transmitter release at a cerebellar synapse

Abstract The manner in which presynaptic Ca 2+ influx controls the release of neurotransmitter was investigated at the granule cell to Purkinje cell synapse in rat cerebellar slices. Excitatory postsynaptic currents were measured using whole-cell voltage clamp, and changes in presynaptic Ca 2+ influx were determined with the Ca 2+ -sensitive dye furaptra. We manipulated presynaptic Ca 2+ entry by altering external Ca 2+ levels and by blocking Ca 2+ channels with Cd 2+ or with the toxins ω-conotoxin GVIA and ω-Aga-IVA. For all of the manipulations, other than the application of ω-Aga-IVA, the relationship between Ca 2+ influx and release was well approximated by a power law, n ≈ 2.5. When ω-AgaIVA was applied, release appeared to be more steeply dependent on Ca 2+ (n ≈ 4), suggesting that ω-Aga-IVA-sensitive channels are more effective at triggering release. Based on interactive effects of toxins on synaptic currents, we conclude that multiple types of Ca 2+ channels synergistically control individual release sites.