Ca~(2+) channel nanodomains boost local Ca~(2+) amplitude

Tadross M.R.; Tsien R.W.; Yue D.T.

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Ca~(2+) channel nanodomains boost local Ca~(2+) amplitude

机译：Ca~(2+) channel nanodomains boost local Ca~(2+) amplitude

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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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第39期|15794-15799|共6页
作者
Tadross M.R.; Tsien R.W.; Yue D.T.;
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作者单位

Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, United States;

Department of Molecular and Cellular Physiology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305, United States;

Calcium Signals Laboratory, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Biosensor; Electrodiffusion; Signaling; Uncaging;

Ca~(2+) channel nanodomains boost local Ca~(2+) amplitude

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