Presynaptic nanodomains : a tale of two synapses
MetadataShow full item record
KeywordNeurotransmitter release; Calcium signaling; Calcium channels; Presynaptic terminals; Synaptic vesicle trafficking
Here we summarize the evidence from two “giant” presynaptic terminals—the squid giant synapse and the mammalian calyx of Held—supporting the involvement of nanodomain calcium signals in triggering of neurotransmitter release. At the squid synapse, there are three main lines of experimental evidence for nanodomain signaling. First, changing the size of the unitary calcium channel current by altering external calcium concentration causes a non-linear change in transmitter release, while changing the number of open channels by broadening the presynaptic action potential causes a linear change in release. Second, low-affinity calcium indicators, calcium chelators, and uncaging of calcium all suggest that presynaptic calcium concentrations are as high as hundreds of micromolar, which is more compatible with a nanodomain type of calcium signal. Finally, neurotransmitter release is much less affected by the slow calcium chelator, ethylene glycol tetraacetic acid (EGTA), in comparison to the rapid chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA). Similarly, as the calyx of Held synapse matures, EGTA becomes less effective in attenuating transmitter release while the number of calcium channels required to trigger a single fusion event declines. This suggests a developmental transformation of microdomain to nanodomain coupling between calcium channels and transmitter release. Calcium imaging and uncaging experiments, in combination with simulations of calcium diffusion, indicate the peak calcium concentration seen by presynaptic calcium sensors reaches at least tens of micromolar at the calyx of Held. Taken together, data from these provide a compelling argument that nanodomain calcium signaling gates very rapid transmitter release.
© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Cellular Neuroscience 8 (2015): 455, doi:10.3389/fncel.2014.00455.
Suggested CitationArticle: Wang, Lu-Yang, Augustine, George J., "Presynaptic nanodomains : a tale of two synapses", Frontiers in Cellular Neuroscience 8 (2015): 455, DOI:10.3389/fncel.2014.00455, https://hdl.handle.net/1912/7231
The following license files are associated with this item:
Showing items related by title, author, creator and subject.
Prolonged calcium influx after termination of light-induced calcium release in invertebrate photoreceptors Gomez, Maria del Pilar; Nasi, Enrico (Rockefeller University Press, 2009-08-31)In microvillar photoreceptors, light stimulates the phospholipase C cascade and triggers an elevation of cytosolic Ca2+ that is essential for the regulation of both visual excitation and sensory adaptation. In some organisms, ...
Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium Schlecker, Christina; Boehmerle, Wolfgang; Jeromin, Andreas; DeGray, Brenda; Varshney, Anurag; Sharma, Yogendra; Szigeti-Buck, Klara; Ehrlich, Barbara E. (American Society for Clinical Investigation, 2006-06)Regulation and dysregulation of intracellular calcium (Ca2+) signaling via the inositol 1,4,5-trisphosphate receptor (InsP3R) has been linked to many cellular processes and pathological conditions. In the present study, ...
Ross, William N. (2012-01)All cells use changes in intracellular calcium concentration [Ca2+]i to regulate cell signaling events In neurons, with their elaborate dendritic and axonal arborizations, there are clear examples of both localized and ...