Effects of 48-Hour Fasting on Intracellular Calcium Homeostasis and the Damage-Recovery Response to Eccentric Contractions in Rat Skeletal Muscle

Background: Short-term fasting, often practiced in weight-category sports, alters whole-body metabolism. However, its impact on skeletal muscle calcium ion (Ca 2+ ) handling is not well understood. Furthermore, the effects of a fasted state on the muscle damage-recovery response following eccentric contractions (ECC) remain to be elucidated. We tested the hypothesis that a 48-hour fast would: 1) lower resting intracellular Ca 2+ concentration ([Ca 2+ ]i) in skeletal muscle, and 2) suppress the progression of inflammatory cell infiltration, an initial response to muscle damage, following ECC. Methods: Adult male Wistar rats were assigned to a control group (CON) or a 48-hour fasting group (48F). Resting [Ca 2+ ]i in the predominantly fast-twitch tibialis anterior (TA) muscle was evaluated via in vivo imaging using the Ca 2+ indicator Fura-2 AM, with the 340/380 nm fluorescence ratio serving as the index of [Ca 2+ ]i. ECC was induced by forced ankle plantar flexion synchronized with electrical stimulation (100 Hz, 0.7 s duration, every 3 s, 40 contractions, 5 sets). Twenty-four hours post-ECC, edema and inflammatory cell infiltration were assessed histologically. Results: Resting [Ca 2+ ]i was significantly lower in the 48F group compared to the CON group (Fura-2 ratio: CON 0.73 ± 0.060 vs. 48F 0.58 ± 0.072, p = 0.0028). No significant differences were observed between groups in the 30-min time course of resting intracellular Ca 2+ levels or in spontaneous Ca 2+ fluctuations measured at rest, indicating that basal Ca 2+ homeostasis was preserved despite the reduced baseline [Ca 2+ ]i. Peak torque during ECC was significantly attenuated by fasting (CON: 16.15 ± 2.25 N vs. 48F: 10.88 ± 1.50 N, p =0.033); however, the total force integral over 5 sets was not different (p = 0.1664). Twenty-four hours post-ECC, inflammatory cell infiltration was markedly suppressed in the 48F group (CON: 16.40 ± 10.60% vs. 48F: 3.80 ± 2.49%, p = 0.0034), whereas no difference was observed in the extent of edema (CON: 19.60 ± 11.35% vs. 48F: 15.20 ± 13.52%, p = 0.5929). These results support that fasting inhibits the transition process from edema to cellular infiltration. Conclusion: In vivo evaluation revealed that 48-hour fasting maintains resting skeletal muscle [Ca 2+ ]i at lower levels. Furthermore, the damage-recovery response to ECC under this condition was characterized by attenuated inflammatory cell infiltration. These findings suggest that fasting modulates early muscle damage responses following ECC. Although the overall force integral during ECC was comparable between groups, the fasted condition was associated with altered Ca 2+ dynamics and reduced peak torque during ECC. The extent to which changes in Ca 2+ handling, contractile characteristics, or their interaction contribute to the attenuation of inflammatory infiltration requires further investigation. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.