OUABAIN-SENSITIVE NA+ K+-ATPASE CONTENT IS ELEVATED IN MDX MICE - IMPLICATIONS FOR THE REGULATION OF IONS IN DYSTROPHIC MUSCLE/

Recent evidence indicates that in dystrophin-deficient muscle, intrace llular sodium content (Na-i) may be elevated and sodium regulation may be altered or impaired. If there is an elevation in Na-i, this could be due to decreased active pumping of sodium from the cell or increase d passive influx of sodium. The present study has therefore determined the content of plasma membrane-bound Na+/K+-ATPase in the skeletal mu scle of mdr mice; a genetically homologous model of Duchenne muscular dystrophy. Measurements were made on muscles from 5-6-month-old mdr mi ce and age-matched controls of the C57B1/1OScSn strain (n = 9 pairs), using the vanadate-facilitated ouabain-binding technique. The Na+/K+-A TPase concentration per unit weight increased by 2.3-fold in the longi ssimus dorsi and 1.4-fold in the gastrocnemius of mdx mice compared wi th controls. The increase in Na+/K+-ATPase content is of similar magni tude to the previously reported increase in ouabain-sensitive Na+/K+-A TPase activity in mdx muscle, suggesting that this elevated enzyme act ivity occurs largely through an increase in its concentration. This co mpensatory increase in the main regulator of internal sodium is likely to occur in an attempt to maintain homeostasis. Nevertheless, the ele vated pump concentration is unable to compensate entirely for the incr eased Na,. These results are consistent with a previously proposed hyp othesis that sodium regulation is abnormal in dystrophin deficient mus cles, and also that cell death in these muscles may be due to abnormal regulation of cell volume.