Résumé :
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A novel E41K beta-tropomyosin mutation, associated with muscle weakness and congenital myopathy, was recently identified. This mutation directly affects contractile characteristics of single skinned muscle fibres, i.e. (i) decreased shortening speeds at saturated Ca2+ concentration (apparent rate constant of force redevelopment ktr and unloaded shortening speed V0); and (ii) depressed sensitivity of force to Ca2+ concentration, contributing to the muscle weakness. To investigate if these mutation-related alterations are reversible, we exposed fibres to the Ca2+ sensitizer EMD 57033 and studied a broad range of contractile parameters. Results showed that 30 µM of EMD 57033 (i) had no effects on shortening speeds at saturated Ca2+ concentration (ktr and V0); but (ii) increased Ca2+ sensitivity of force, in fibres carrying the E41K beta-Tm mutation, emphasizing a potential therapeutic role of this drug in patients carrying the mutation. To improve the understanding of the mechanisms underlying the improvement in Ca2+ sensitivity of force in fibres exposed to EMD 57033, stiffness was evaluated in various Ca2+ concentrations. Ca2+ sensitivity of stiffness was also enhanced after exposure to the Ca2+ sensitizer, suggesting that the changes in the Ca2+ activation of force were predominantly due to an increase in the relative number of attached cross-bridges at different Ca2+ concentrations.
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