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Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells

Author

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  • Shi-Qiang Wang

    (Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health)

  • Long-Sheng Song

    (Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health)

  • Edward G. Lakatta

    (Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health)

  • Heping Cheng

    (Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health
    National Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University)

Abstract

Ca2+-induced Ca2+ release is a general mechanism that most cells use to amplify Ca2+ signals1,2,3,4,5. In heart cells, this mechanism is operated between voltage-gated L-type Ca2+ channels (LCCs) in the plasma membrane and Ca2+ release channels, commonly known as ryanodine receptors, in the sarcoplasmic reticulum3,4,5. The Ca2+ influx through LCCs traverses a cleft of roughly 12 nm formed by the cell surface and the sarcoplasmic reticulum membrane, and activates adjacent ryanodine receptors to release Ca2+ in the form of Ca2+ sparks6. Here we determine the kinetics, fidelity and stoichiometry of coupling between LCCs and ryanodine receptors. We show that the local Ca2+ signal produced by a single opening of an LCC, named a ‘Ca2+ sparklet’, can trigger about 4–6 ryanodine receptors to generate a Ca2+ spark. The coupling between LCCs and ryanodine receptors is stochastic, as judged by the exponential distribution of the coupling latency. The fraction of sparklets that successfully triggers a spark is less than unity and declines in a use-dependent manner. This optical analysis of single-channel communication affords a powerful means for elucidating Ca2+-signalling mechanisms at the molecular level.

Suggested Citation

  • Shi-Qiang Wang & Long-Sheng Song & Edward G. Lakatta & Heping Cheng, 2001. "Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells," Nature, Nature, vol. 410(6828), pages 592-596, March.
    • Handle: RePEc:nat:nature:v:410:y:2001:i:6828:d:10.1038_35069083
    DOI: 10.1038/35069083
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    Cited by:

    1. Vijay Rajagopal & Gregory Bass & Cameron G Walker & David J Crossman & Amorita Petzer & Anthony Hickey & Ivo Siekmann & Masahiko Hoshijima & Mark H Ellisman & Edmund J Crampin & Christian Soeller, 2015. "Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes," PLOS Computational Biology, Public Library of Science, vol. 11(9), pages 1-31, September.
    2. Peter Sidaway & Noriyoshi Teramoto, 2014. "L-Type Ca2+ Channel Sparklets Revealed by TIRF Microscopy in Mouse Urinary Bladder Smooth Muscle," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-11, April.

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