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Research Article Free access | 10.1172/JCI117393

Ca2+ homeostasis in Brody's disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil.

A A Benders, J H Veerkamp, A Oosterhof, P J Jongen, R J Bindels, L M Smit, H F Busch, and R A Wevers

Department of Biochemistry, University of Nijmegen, The Netherlands.

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Department of Biochemistry, University of Nijmegen, The Netherlands.

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Department of Biochemistry, University of Nijmegen, The Netherlands.

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Department of Biochemistry, University of Nijmegen, The Netherlands.

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Department of Biochemistry, University of Nijmegen, The Netherlands.

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Department of Biochemistry, University of Nijmegen, The Netherlands.

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Department of Biochemistry, University of Nijmegen, The Netherlands.

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Department of Biochemistry, University of Nijmegen, The Netherlands.

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Published August 1, 1994 - More info

Published in Volume 94, Issue 2 on August 1, 1994
J Clin Invest. 1994;94(2):741–748. https://doi.org/10.1172/JCI117393.
© 1994 The American Society for Clinical Investigation
Published August 1, 1994 - Version history
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Abstract

Brody's disease, i.e., sarcoplasmic reticulum (SR) Ca(2+)-dependent Mg(2+)-ATPase (Ca(2+)-ATPase) deficiency, is a rare inherited disorder of skeletal muscle function. Pseudo-myotonia is the most important clinical feature. SR Ca(2+)-ATPase and Ca2+ homeostasis are examined in m. quadriceps and/or cultured muscle cells of controls and 10 patients suffering from Brody's disease. In both m. quadriceps and cultured muscle cells of patients, the SR Ca(2+)-ATPase activity is decreased by approximately 50%. However, the concentration of SR Ca(2+)-ATPase and SERCA1 are normal. SERCA1 accounts for 83 and 100% of total SR Ca(2+)-ATPase in m. quadriceps and cultured muscle cells, respectively. This implies a reduction of the molecular activity of SERCA1 in Brody's disease. The cytosolic Ca2+ concentration ([Ca2+]i) at rest and the increase of [Ca2+]i after addition of acetylcholine are the same in cultured muscle cells of controls and patients. The half-life of the maximal response, however, is raised three times in the pathological muscle cells. Addition of dantrolene or verapamil after the maximal response accelerates the restoration of the [Ca2+]i in these muscle cells. The differences in Ca2+ handling disappear by administration of dantrolene or verapamil concomitantly with acetylcholine. The reduced Ca2+ re-uptake from the cytosol presumably due to structural modification(s) of SERCA1 may explain the pseudo-myotonia in Brody's disease. Single cell measurements suggest a beneficial effect of dantrolene or verapamil in treating patients suffering from Brody's disease.

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