Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels

作者：Ermolyuk Yaroslav S; Alder Felicity G; Surges Rainer; Pavlov Ivan Y; Timofeeva Yulia; Kullmann Dimitri M; Volynski Kirill E^*

来源：Nature Neuroscience, 2013, 16(12): 1754-1763.

DOI：10.1038/nn.3563

The role of voltage-gated Ca2+ channels (VGCCs) in spontaneous miniature neurotransmitter release is incompletely understood. We found that stochastic opening of P/Q-, N- and R-type VGCCs accounts for -50% of all spontaneous glutamate release at rat cultured hippocampal synapses, and that R-type channels have a far greater role in spontaneous than in action potentialevoked exocytosis. VGCC-dependent miniature neurotransmitter release (minis) showed similar sensitivity to presynaptic Ca2+ chelation as evoked release, arguing for direct triggering of spontaneous release by transient spatially localized Ca2+ domains. Experimentally constrained three-dimensional diffusion modeling of Ca2+ influx-exocytosis coupling was consistent with clustered distribution of VGCCs in the active zone of small hippocampal synapses and revealed that spontaneous VGCCs openings can account for the experimentally observed VGCC-dependent minis, although single channel openings triggered release with low probability. Uncorrelated stochastic VGCC opening is therefore a major trigger for spontaneous glutamate release, with differential roles for distinct channel subtypes.

• 出版日期2013-12