Live-cell photo-activated localization microscopy correlates nanoscale ryanodine receptor configuration to calcium sparks in cardiomyocytes.

Autor: Hou Y; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway., Laasmaa M; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway., Li J; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway., Shen X; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway., Manfra O; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway., Norden ES; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo Norway., Le C; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway., Zhang L; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo Norway., Sjaastad I; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo Norway., Jones PP; Department of Physiology, School of Biomedical Sciences and HeartOtago, University of Otago, Dunedin, New Zealand., Soeller C; Department of Physiology, University of Bern, Bern, Switzerland., Louch WE; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, NO-0424 Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo Norway.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2023 Mar 15; Vol. 2 (3), pp. 251-267.
DOI: 10.1038/s44161-022-00199-2
Abstrakt: Ca 2+ sparks constitute the fundamental units of Ca 2+ release in cardiomyocytes. Here we investigate how ryanodine receptors (RyRs) collectively generate these events by employing a transgenic mouse with a photo-activated label on RyR2. This allowed correlative imaging of RyR localization, by super-resolution Photo-Activated Localization Microscopy, and Ca 2+ sparks, by high-speed imaging. Two populations of Ca 2+ sparks were observed: stationary events and "travelling" events that spread between neighbouring RyR clusters. Travelling sparks exhibited up to 8 distinct releases, sourced from local or distal junctional sarcoplasmic reticulum. Quantitative analyses showed that sparks may be triggered by any number of RyRs within a cluster, and that acute β-adrenergic stimulation augments intra-cluster RyR recruitment to generate larger events. In contrast, RyR "dispersion" during heart failure facilitates the generation of travelling sparks. Thus, RyRs cooperatively generate Ca 2+ sparks in a complex, malleable fashion, and channel organization regulates the propensity for local propagation of Ca 2+ release.
Competing Interests: Competing Interests Statement The authors declare no competing interests.
Databáze: MEDLINE
Externí odkaz: