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Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised
Author(s) -
Warskulat Ulrich,
Flögel Ulrich,
Jacoby Christoph,
Hartwig HansGeorg,
Thewissen Michael,
Merx Marc W.,
Molojavyi Andrej,
HellerStilb Birgit,
Schrader Jürgen,
Häussinger Dieter
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0496fje
Subject(s) - taurine , skeletal muscle , medicine , endocrinology , cardiac muscle , osmolyte , chemistry , cardiac function curve , knockout mouse , biochemistry , biology , heart failure , amino acid , receptor
Taurine is the most abundant free amino acid in heart and skeletal muscle. In the present study, the effects of hereditary taurine deficiency on muscle function were examined in taurine transporter knockout ( taut −/−) mice. These mice show an almost complete depletion of heart and skeletal muscle taurine levels. Treadmill experiments demonstrated that total exercise capacity of taut −/− mice was reduced by >80% compared with wild‐type controls. The decreased performance of taut −/− mice correlated with increased lactate levels in serum during exercise. Surprisingly, cardiac function of taut −/− mice as assessed by magnetic resonance imaging, echocardiography, and isolated heart studies showed a largely normal phenotype under both control and stimulated conditions. However, analysis of taut −/− skeletal muscle revealed electromyographic abnormalities. 1 H nuclear magnetic resonance spectroscopy of tissue extracts showed that in the heart of taut −/− mice the lack of taurine was compensated by the up‐regulation of various organic solutes. In contrast, a deficit of >10 mM in total organic osmolyte concentration was found in skeletal muscle. The present study identifies taurine transport as a crucial factor for the maintenance of skeletal muscle function and total exercise capacity, while cardiac muscle apparently can compensate for the loss of taurine.