Creatine supplementation upregulates excitation-contraction coupling in C2C12 myotubes
Aida Calderón-Rivera, Ana Victoria Vega, Guillermo Avila
Department of Biochemistry, Cinvestav-IPN, Mexico City, Mexico
Abstract: The main goal of this work was to investigate whether creatine (Cr) might be able to regulate skeletal muscle excitation-contraction (EC) coupling. Myotubes from a C2C12 cell line were exposed to Cr (25 mM, 2–4 hours). Subsequently, the activity of L-type Ca2+ channels and voltage-gated Ca2+ release (VGCR) were investigated using the whole-cell patch-clamp technique. Cr upregulated VGCR by 2.4-fold, in the absence of major alterations in L-type Ca2+ channel activity, the extent of caffeine-induced sarcoplasmic reticulum Ca2+ release, or the termination kinetics of Ca2+ transients. Thus, stimulation of VGCR cannot be explained by upregulation of the activity of either L-type Ca2+ channels or sarcoplasmic reticulum Ca2+-ATPase. We also investigated possible long-term regulation of L-type Ca2+ channels by Cr. However, chronic treatment with Cr (2–4 days) affected neither the density of ICaL nor the corresponding voltagedependence of activation. The later result was obtained in the face of a 1.7-fold stimulation of myogenesis. Therefore, it cannot be explained by possible desensitization of Cr metabolism. These data could suggest that the functional expression of L-type Ca2+ channels is not affected by prior acute stimulation of VGCR. Previous work has shown that Cr supplementation enhances muscle strength. Thus, it will be interesting to investigate whether this effect can be at least partially explained by acute stimulation of VGCR.
Keywords: L-type calcium channel, ryanodine receptor, intracellular calcium
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