Defective regulation of contractile function in muscle fibres carrying an E41K β-tropomyosin mutation

• Published in: The Journal of physiology 2008-06, Vol.586 (12), p.2993
• Main Authors: Julien Ochala, Meishan Li, Monica Ohlsson, Anders Oldfors, Lars Larsson
• Format: Article
• Language: English
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2008.153650

A novel E41K β-tropomyosin (β-Tm) mutation, associated with congenital myopathy and muscle weakness, was recently identified in a woman and her daughter. In both patients, muscle weakness was coupled with muscle fibre atrophy. It remains unknown, however, whether the E41K β-Tm mutation directly affects regulation of muscle contraction, contributing to the muscle weakness. To address this question, we studied a broad range of contractile characteristics in skinned muscle fibres from the two patients and eight healthy controls. Results showed decreases (i) in speed of contraction at saturated Ca 2+ concentration (apparent rate constant of force redevelopment ( k tr ) and unloaded shortening speed ( V 0 )); and (ii) in contraction sensitivity to Ca 2+ concentration, in fibres from patients compared with controls, suggesting that the mutation has a negative effect on contractile function, contributing to the muscle weakness. To investigate whether these negative impacts are reversible, we exposed skinned muscle fibres to the Ca 2+ sensitizer EMD 57033. In fibres from patients, 30 μ m of EMD 57033 (i) had no effect on speed of contraction ( k tr and V 0 ) at saturated Ca 2+ concentration but (ii) increased Ca 2+ sensitivity of contraction, suggesting a potential therapeutic approach in patients carrying the E41K β-Tm mutation.