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Ca<jats:sup>2+<\/jats:sup> is a vital signaling messenger that regulates multiple cellular processes via its spatial and temporal concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) dynamics. We hypothesized that 1) a specific pattern of spatial\/temporal intramyocyte Ca<jats:sup>2+<\/jats:sup> dynamics portends muscle damage following ECC and 2) these dynamics would be regulated by the ryanodine receptor (RyR). [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in the tibialis anterior muscles of anesthetized adult Wistar rats was measured by ratiometric (i.e., ratio, R, 340\/380 nm excitation) in vivo bioimaging with Fura-2 pre-ECC and at 5 and 24 h post-ECC (5 \u00d7 40 contractions). Separate groups of rats received RyR inhibitor dantrolene (DAN; 10 mg\/kg ip) immediately post-ECC (+DAN). Muscle damage was evaluated by histological analysis on hematoxylin-eosin stained muscle sections. Compared with control (CONT, no ECC), [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> distribution was heterogeneous with increased percent total area of high [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> sites (operationally defined as R \u2265 1.39, i.e., \u22651 SD of mean control) 5 h post-ECC (CONT, 14.0\u2009\u00b1\u20098.0; ECC5h: 52.0\u2009\u00b1\u20097.4%, P &lt; 0.01). DAN substantially reduced the high [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> area 5 h post-ECC (ECC5h + DAN: 6.4\u2009\u00b1\u20093.1%, P &lt; 0.01) and myocyte damage (ECC24h, 63.2\u2009\u00b1\u20091.0%; ECC24h + DAN: 29.1\u2009\u00b1\u20092.2%, P &lt; 0.01). Temporal and spatially amplified [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> fluctuations occurred regardless of DAN (ECC vs. ECC + DAN, P &gt; 0.05). These results suggest that the RyR-mediated local high [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> itself is related to the magnitude of muscle damage, whereas the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> fluctuation is an RyR-independent phenomenon. <\/jats:p>","DOI":"10.1152\/ajpregu.00166.2021","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T13:00:54Z","timestamp":1636549254000},"page":"R14-R27","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Ryanodine receptors mediate high intracellular Ca<sup>2+<\/sup> and some myocyte damage following eccentric contractions in rat fast-twitch skeletal muscle"],"prefix":"10.1152","volume":"322","author":[{"given":"Ayaka","family":"Tabuchi","sequence":"first","affiliation":[{"name":"Department of Engineering Science, Bioscience and Technology Program, University of Electro-Communications, Chofu, 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