Sarcoplasmic reticulum calcium handling in unbranched, immediately post-necrotic fast-twitch mdx fibres is similar to wild-type littermates

Abstract

New findings: What is the central question of this study? What are the early effects of dystrophin deficiency on sarcoplasmic reticulum Ca²⁺ handling in the mdx mouse? What is the main finding and its importance? In the mdx mouse, Ca²⁺ handling by the sarcoplasmic reticulum is little affected by the absence of dystrophin when looking at fibres without branches that have recently regenerated after massive myonecrosis. This has important implications for our understanding of Ca²⁺ pathology in the mdx mouse.

Abstract: There is a variety of results in the literature regarding the effects of dystrophin deficiency on the Ca²⁺ handling properties of the sarcoplasmic reticulum (SR) in the mdx mouse, an animal model of Duchenne muscular dystrophy. One possible source of variation is the presence of branched fibres. Fibre branching, a consequence of degenerative-regenerative processes such as muscular dystrophy, has in itself a significant influence on the function of the SR. In this study, we attempted to detect early effects of dystrophin deficiency on SR Ca²⁺ handling by using unbranched fibres from the immediate post-necrotic stage in mdx mice (recently regenerated after massive necrosis). Using kinetically corrected fura-2 fluorescence signals measured during twitch and tetanus, we analysed the amplitude, rise time and decay time of Δ[Ca²⁺ ]_i in unfatigued and fatigued fibres. Decay was also resolved into SR pump and SR leak components. Fibres from mdx mice were similar in all respects to fibres from wild-type littermates apart from: (1) a smaller amplitude of the initial spike of Δ[Ca²⁺ ]_i during a tetanus; and (2) a mitigation of the fall in Δ[Ca²⁺ ]_i amplitude during the course of fatigue. Our findings suggest that the early effects of a loss of dystrophin on SR Ca²⁺ handling in mdx mice are subtle, and we emphasize the importance of distinguishing between Ca²⁺ pathology that is attributable to lack of dystrophin and Ca²⁺ pathology that is attributable to muscle degeneration.

Keywords: branched fibres; mdx mouse; sarcoplasmic reticulum calcium.