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Acta Physiologica 2007; Volume 191, Supplement 660
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Autumn Meeting 2006
11/18/2006-11/18/2006
”Université Libre de Bruxelles”, Brussels, Belgium
CALCIUM ENTRY THROUGH STORE-OPERATED AND MECHANOSENSITIVE CHANNELS ACTIVATES CALPAIN IN NORMAL AND DYSTROPHIC SKELETAL MUSCLE FIBRES.
Abstract number: P-09
Gailly1 P, De Backer1 F., Van Schoor1 M., Gillis1 J.M.
1Catholic University of Louvain. Laboratory of Cell Physiology. 55/40 av. Hippocrate 1200 Brussels, Belgium
Duchenne muscular dystrophy is due to the loss of dystrophin, a cytoskeletal protein associated with the inner surface membrane, in skeletal muscle. The absence of dystrophin induces an abnormal influx of calcium through cationic channels in muscle fibres from dystrophic (mdx) mice. We previously showed that these channels belong to the Transient Receptor Potential (TRP) family and were activated by store depletion (SOC: Store Operated Channel) and by membrane stretch (SAC: Stretch Activated Channel).
Proteolysis has been reported to be increased in mdx muscle fibres, a situation that is corrected when extracellular calcium concentration is decreased by a factor of 10. This could be due to a higher basal activity of m- and/or m-calpains, two ubiquitous cysteine proteases. However, these two enzymes are known to be sensitive to [Ca2+]i in the micromolar and millimolar range and are thus not expected tot be activated under physiological conditions. Here, by using a fluorescent-based technique, we detected a calpain activity in situ in muscle fibres. Interestingly, WB analysis showed that a small proportion of calpain protein was autolyzed (around 10% of total calpain) in a 78kDa fragment which has been shown to be more sensitive to calcium and which binds to the plasma membrane. We confirm that mdx fibres present a higher calpain activity than control fibres. We also show that [Ca2+]i transients related to normal physiological stimulations (twitch and tetanus contractions) are not associated to an increased calpain activity. However, manoeuvers that trigger calcium influxes through SOCs or SACs resulting in prolonged elevations of [Ca2+]i increase calpain activity. This emphasizes the importance of the time scale (minutes) and/or the localization (submembranous) of [Ca2+]i transients in the activation of a specific target like calpain.
Our data support the hypothesis that the higher protease activity observed in mdx muscles might be related, at least partially, to the activation of calpains by cytosolic calcium entering the cell through SOCs and/or SACs,
To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 191, Supplement 660 :P-09