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Ca2+ channel nanodomains boost local Ca2+ amplitude.

dc.contributor.author Tadross, Michael Raphael
dc.contributor.author Tsien, RW
dc.contributor.author Yue, DT
dc.coverage.spatial United States
dc.date.accessioned 2017-09-19T16:42:34Z
dc.date.available 2017-09-19T16:42:34Z
dc.date.issued 2013-09-24
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/24019485
dc.identifier 1313898110
dc.identifier.uri http://hdl.handle.net/10161/15559
dc.description.abstract Local Ca(2+) signals through voltage-gated Ca(2+) channels (CaVs) drive synaptic transmission, neural plasticity, and cardiac contraction. Despite the importance of these events, the fundamental relationship between flux through a single CaV channel and the Ca(2+) signaling concentration within nanometers of its pore has resisted empirical determination, owing to limitations in the spatial resolution and specificity of fluorescence-based Ca(2+) measurements. Here, we exploited Ca(2+)-dependent inactivation of CaV channels as a nanometer-range Ca(2+) indicator specific to active channels. We observed an unexpected and dramatic boost in nanodomain Ca(2+) amplitude, ten-fold higher than predicted on theoretical grounds. Our results uncover a striking feature of CaV nanodomains, as diffusion-restricted environments that amplify small Ca(2+) fluxes into enormous local Ca(2+) concentrations. This Ca(2+) tuning by the physical composition of the nanodomain may represent an energy-efficient means of local amplification that maximizes information signaling capacity, while minimizing global Ca(2+) load.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.relation.isversionof 10.1073/pnas.1313898110
dc.subject biosensor
dc.subject electrodiffusion
dc.subject signaling
dc.subject uncaging
dc.subject Calcium
dc.subject Calcium Channels
dc.subject Calcium Signaling
dc.subject Calibration
dc.subject HEK293 Cells
dc.subject Humans
dc.subject Ion Channel Gating
dc.subject Models, Biological
dc.subject Protein Structure, Tertiary
dc.title Ca2+ channel nanodomains boost local Ca2+ amplitude.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/24019485
pubs.begin-page 15794
pubs.end-page 15799
pubs.issue 39
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Duke
pubs.organisational-group Pratt School of Engineering
pubs.publication-status Published
pubs.volume 110
dc.identifier.eissn 1091-6490


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