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, intracellular 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 increased passive influx of sodium. The present study has therefore determined the content of plasma membrane-bound Na+/K(+)-ATPase in the skeletal muscle of mdx mice; a genetically homologous model of Duchenne muscular dystrophy. Measurements were made on muscles from 5-6-month-old mdx mice and age-matched controls of the C57B1/10ScSn strain (n = 9 pairs), using the vanadate-facilitated ouabain-binding technique. The Na+/K(+)-ATPase concentration per unit weight increased by 2.3-fold in the longissimus dorsi and 1.4-fold in the gastrocnemius of mdx mice compared with controls. The increase in Na+/K(+)-ATPase content is of similar magnitude to the previously reported increase in ouabain-sensitive Na+/K(+)-ATPase activity in mdx muscle, suggesting that this elevated enzyme activity occurs largely through an increase in its concentration. This compensatory increase in the main regulator of internal sodium is likely to occur in an attempt to maintain homeostasis. Nevertheless, the elevated pump concentration is unable to compensate entirely for the increased Na(i). These results are consistent with a previously proposed hypothesis that sodium regulation is abnormal in dystrophin deficient muscles, and also that cell death in these muscles may be due to abnormal regulation of cell volume.
Dunn
J F
JF
MRC Biochemical and Clinical Magnetic Resonance Unit, Oxford, UK. jeff.dunn@dartmouth.edu
Burton
K A
KA
Dauncey
M J
MJ
D000818:Animals; D016189:Dystrophin / Q000172:deficiency; D066298:In Vitro Techniques; D051379:Mice; D008818:Mice, Neurologic Mutants; D018482:Muscle, Skeletal / Q000201:enzymology / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism
D016189:Dystrophin; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase