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Defective regulation of contractile function in muscle fibres carrying an E41K β‐tropomyosin mutation
Author(s) -
Ochala Julien,
Li Meishan,
Ohlsson Monica,
Oldfors Anders,
Larsson Lars
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.153650
Subject(s) - contraction (grammar) , muscle contraction , medicine , muscle weakness , weakness , tropomyosin , endocrinology , chemistry , muscle fatigue , myopathy , actin , anatomy , biology , biochemistry , electromyography , neuroscience
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.