title: Ca2+ channel nanodomains boost local Ca2+ amplitude.
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.
authors.affiliation: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tadross
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsien
authors.forename: David T
authors.initials: DT
authors.lastname: Yue
mesh_terms: D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism*; D020013:Calcium Signaling; D002138:Calibration; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D008954:Models, Biological; D017434:Protein Structure, Tertiary
chemical_list: D015220:Calcium Channels; D002118:Calcium
keywords: biosensor; electrodiffusion; signaling; uncaging
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