期刊
PHYSIOLOGICAL REPORTS
卷 5, 期 5, 页码 -出版社
WILEY
DOI: 10.14814/phy2.13180
关键词
Ca2+-induc Ca2+ release; ryanodine receptor; sarcoplasmic reticulum; store overload-induced Ca2+ release
类别
资金
- Japan Society for the Promotion of Science [22300221, 2365043, 16H03240]
- Nakatomi Foundation
- Grants-in-Aid for Scientific Research [16H03240, 22300221] Funding Source: KAKEN
In contrast to cardiomyocytes, store overload-induced calcium ion (Ca2+) release (SOICR) is not considered to constitute a primary Ca2+ releasing system from the sarcoplasmic reticulum (SR) in skeletal muscle myocytes. In the latter, voltage-induced Ca2+ release (VICR) is regarded as the dominant mechanism facilitating contractions. Any role of the SOICR in the regulation of cytoplasmic Ca2+ concentration ([Ca2+](i)) and its dynamics in skeletal muscle in vivo remains poorly understood. By means of in vivo single fiber Ca2+ microinjections combined with bioimaging techniques, we tested the hypothesis that the [Ca2+](i) dynamics following Ca2+ injection would be amplified and fiber contraction facilitated by SOICR. The circulation-intact spinotrapezius muscle of adult male Wistar rats (n = 34) was exteriorized and loaded with Fura-2 AM to monitor [Ca2+](i) dynamics. Groups of rats underwent the following treatments: (1) 0.02, 0.2, and 2.0 mmol/L Ca2+ injections, (2) 2.0 mmol/L Ca2+ with inhibition of ryanodine receptors (RyR) by dantrolene sodium (DAN), and (3) 2.0 mmol/L Ca2+ with inhibition of SR Ca2+ ATPase (SERCA) by cyclopiazonic acid (CPA). A quantity of 0.02 mmol/L Ca2+ injection yielded no detectable response, whereas peak evoked [Ca2+](i) increased 9.9 +/- 1.8% above baseline for 0.2 mmol/L and 23.8 c 4.3% (P < 0.05) for 2.0 mmol/L Ca2+ injections. The peak [Ca2+](i) in response to 2.0 mmol/L Ca2+ injection was largely abolished by DAN and CPA (-85.8%, -71.0%, respectively, both P < 0.05 vs. unblocked) supporting dependence of the [Ca2+](i) dynamics on Ca2+ released by SOICR rather than injected Ca2+ itself. Thus, this investigation demonstrates the presence of a robust SR-evoked SOICR operant in skeletal muscle in vivo.
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