In vivo Ca(2+) dynamics induced by Ca(2+) injection in individual rat skeletal muscle fibers

In contrast to cardiomyocytes, store overload‐induced calcium ion (Ca(2+)) release (SOICR) is not considered to constitute a primary Ca(2+) releasing system from the sarcoplasmic reticulum (SR) in skeletal muscle myocytes. In the latter, voltage‐induced Ca(2+) release (VICR) is regarded as the dominant mechanism facilitating contractions. Any role of the SOICR in the regulation of cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) and its dynamics in skeletal muscle in vivo remains poorly understood. By means of in vivo single fiber Ca(2+) microinjections combined with bioimaging techniques, we tested the hypothesis that the [Ca(2+)](i) dynamics following Ca(2+) 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 [Ca(2+)](i) dynamics. Groups of rats underwent the following treatments: (1) 0.02, 0.2, and 2.0 mmol/L Ca(2+) injections, (2) 2.0 mmol/L Ca(2+) with inhibition of ryanodine receptors (RyR) by dantrolene sodium (DAN), and (3) 2.0 mmol/L Ca(2+) with inhibition of SR Ca(2+) ATPase (SERCA) by cyclopiazonic acid (CPA). A quantity of 0.02 mmol/L Ca(2+) injection yielded no detectable response, whereas peak evoked [Ca(2+)](i) increased 9.9 ± 1.8% above baseline for 0.2 mmol/L and 23.8 ± 4.3% (P < 0.05) for 2.0 mmol/L Ca(2+) injections. The peak [Ca(2+)](i) in response to 2.0 mmol/L Ca(2+) injection was largely abolished by DAN and CPA (−85.8%, −71.0%, respectively, both P < 0.05 vs. unblocked) supporting dependence of the [Ca(2+)](i) dynamics on Ca(2+) released by SOICR rather than injected Ca(2+) itself. Thus, this investigation demonstrates the presence of a robust SR‐evoked SOICR operant in skeletal muscle in vivo.