Synaptic Transmission

Willing to Fuse

Science's STKE  31 May 2005:
Vol. 2005, Issue 286, pp. tw206
DOI: 10.1126/stke.2862005tw206

Lou et al. investigated the effect of phorbol esters on neurotransmitter release at the calyx of Held, a central synapse with a giant presynaptic nerve terminal. Phorbol-12,13-dibutyrate (PDBu) increased the amplitude of evoked excitatory postsynaptic currents (EPSCs) and the frequency of spontaneous miniature EPSCs (mEPSCs) without affecting mEPSC amplitude (indicating a presynaptic mechanism). When release was evoked by photolysis of "caged" presynaptic Ca2+, the EPSC amplitudes and peak release rate evoked by weak Ca2+-uncaging stimuli (2.5 to 5 μM presynaptic [Ca2+]i) were markedly potentiated by PDBu, whereas those evoked by strong Ca2+ -uncaging stimuli (10 to 13 μM presynaptic [Ca2+]i) were not. Moreover, PDBu increased the frequency of mEPSCs at basal [Ca2+]i without affecting [Ca2+]i.. Measurement of release at near-basal [Ca2+]i indicated that, surprisingly, the Ca2+ cooperativity of release was low at [Ca2+]i values below 3 μM compared with that at higher concentrations. Modeling the data led the authors to propose an allosteric model in which vesicle fusion can occur even in the absence of bound Ca2+, with the rate of fusion increasing with increased occupancy of the Ca2+ sensor. In this model, phorbol esters enhance the basal "willingness" of vesicles to fuse with the cell membrane, an effect that the authors suggest could explain the link between increases in evoked and spontaneous release seen in many forms of synaptic plasticity.

X. Lou, V. Scheuss, R. Schneggenburger, Allosteric modulation of the presynaptic Ca2+ sensor for vesicle fusion. Nature 435, 497-501 (2005). [PubMed]