Live-cell photoactivated localization microscopy correlates nanoscale ryanodine receptor configuration to calcium sparks in cardiomyocytes
نویسندگان
چکیده
Abstract Ca 2+ sparks constitute the fundamental units of release in cardiomyocytes. Here we investigate how ryanodine receptors (RyRs) collectively generate these events by employing a transgenic mouse with photoactivated label on RyR2. This allowed correlative imaging RyR localization, super-resolution localization microscopy, and sparks, high-speed imaging. Two populations were observed: stationary ‘traveling’ that spread between neighboring clusters. Traveling exhibited up to eight distinct releases, sourced from local or distal junctional sarcoplasmic reticulum. Quantitative analyses showed may be triggered any number RyRs within cluster, acute ?-adrenergic stimulation augments intracluster recruitment larger events. In contrast, ‘dispersion’ during heart failure facilitates generation traveling sparks. Thus, cooperatively complex, malleable fashion, channel organization regulates propensity for propagation release.
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ژورنال
عنوان ژورنال: Nature Cardiovascular Research
سال: 2023
ISSN: ['2731-0590']
DOI: https://doi.org/10.1038/s44161-022-00199-2