Rybalka, Emma ORCID: 0000-0002-4854-0036, Carey, Michael F and Hayes, Alan ORCID: 0000-0003-1398-3694 (2002) Creatine supplementation improves sarcoplasmic reticulum function in dystrophic skeletal muscle. In: Australian Physiological and Pharmacological Society Meeting (69th), 200, 25 November 2002-27 November 2002, Melbourne.

Abstract

Since the progressive degeneration characteristic of dystrophic disease is governed by the Ca2+-induced damage cycle, improving the Ca2+ handling capacity of dystrophin-deficient muscle could be of potential therapeutic benefit. Pulido et al.1 have shown increased survival of dystrophic mdx myotubes following creatine pre-treatment that was associated with decreased intracellular Ca2+ concentrations. This was attributed to improved sarcoplasmic reticulum (SR) Ca2+ ATPase function, although this was not measured. Thus, we have investigated SR Ca2+ uptake activity in mdx skeletal muscle following dietary creatine supplementation. Female mdx mice were randomly separated into non-supplemented (n=8) and creatine-supplemented (n=8) groups. A third group of normal mice (C57BL/10ScCn) was used for comparisons between normal and dystrophic animals (n=8). Creatine was administered reconstituted in normal chow over a 6-week period. On the day of experimentation, animals were anaethetised with sodium pentobarbitone (60 mg/kg body weight; i.p.) and the tibialis anterior (TA) and diaphragm excised. SR Ca2+ uptake rate was measured spectrofluorometrically in homogenized vesicle preparations using the Ca2+-specific fluorophore Fura-2. SR Ca2+ uptake rate was significantly faster in unsupplemented dystrophic muscle (P<0.05) compared to normal muscles, and notably faster in diaphragm than TA (P<0.01). SR Ca2+ uptake rate was further increased after creatine treatment in both TA and diaphragm (P<0.01) compared with unsupplemented muscle, and again faster in diaphragm compared with TA (P<0.05). These results indicate that ATP-supported SR Ca2+ uptake is already up-regulated in dystrophic muscle, most likely in response to the high intracellular Ca2+ environment. Dietary creatine supplementation further improved SR Ca2+ uptake activity by increasing ATP availability to the Ca2+-ATPase pump, and could thus potentially be used as a therapeutic adjunct for the treatment of muscular dystrophy. (1) Pulido SM, Passaquin AC, Leijendekker WJ, Challet C, Wallimann T, Ruegg UT. FEBS. 1998;439:357-362.

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