Barium chloride injures myofibers through calcium-induced proteolysis with fragmentation of motor nerves and microvessels. Academic Article uri icon


  • BACKGROUND: Local injection of BaCl2 is an established model of acute injury to study the regeneration of skeletal muscle. However, the mechanism by which BaCl2 causes muscle injury is unresolved. Because Ba2+ inhibits K+ channels, we hypothesized that BaCl2 induces myofiber depolarization leading to Ca2+ overload, proteolysis, and membrane disruption. While BaCl2 spares resident satellite cells, its effect on other tissue components integral to contractile function has not been defined. We therefore asked whether motor nerves and microvessels, which control and supply myofibers, are injured by BaCl2 treatment. METHODS: The intact extensor digitorum longus (EDL) muscle was isolated from male mice (aged 3-4months) and irrigated with physiological salt solution (PSS) at 37C. Myofiber membrane potential (Vm) was recorded using sharp microelectrodes while intracellular calcium concentration ([Ca2+]i) was evaluated with Fura 2 dye. Isometric force production of EDL was measured in situ, proteolytic activity was quantified by calpain degradation of II-spectrin, and membrane disruption was marked by nuclear staining with propidium iodide (PI). To test for effects on motor nerves and microvessels, tibialis anterior or gluteus maximus muscles were injected with 1.2% BaCl2 (50-75L) in vivo followed by immunostaining to evaluate the integrity of respective tissue elements post injury. Data were analyzed using Students t test and analysis of variance with P0.05 considered statistically significant. RESULTS: Addition of 1.2% BaCl2 to PSS depolarized myofibers from -793mV to -177mV with a corresponding rise in [Ca2+]i; isometric force transiently increased from 7.40.1g to 11.10.4g. Following 1h of BaCl2 exposure, 923% of myonuclei stained with PI (vs. 83% in controls) with enhanced cleavage of II-spectrin. Eliminating Ca2+ from PSS prevented the rise in [Ca2+]i and ameliorated myonuclear staining with PI during BaCl2 exposure. Motor axons and capillary networks appeared fragmented within 24h following injection of 1.2% BaCl2 and morphological integrity deteriorated through 72h. CONCLUSIONS: BaCl2 injures myofibers through depolarization of the sarcolemma, causing Ca2+ overload with transient contraction, leading to proteolysis and membrane rupture. Motor innervation and capillarity appear disrupted concomitant with myofiber damage, further compromising muscle integrity.

published proceedings

  • Skelet Muscle

author list (cited authors)

  • Morton, A. B., Norton, C. E., Jacobsen, N. L., Fernando, C. A., Cornelison, D., & Segal, S. S.

complete list of authors

  • Morton, Aaron B||Norton, Charles E||Jacobsen, Nicole L||Fernando, Charmain A||Cornelison, DDW||Segal, Steven S

publication date

  • November 2019