Alterations in the properties and isoforms of sciatic nerve Na(+), K(+)-ATPase in methylcyclopentadienyl manganese tricarbonyl-treated mice

The in vivo effect of methylcyclopentadienyl manganese tricarbonyl (MMT), an organic manganese-containing compound, on the mouse motor nerve was studied. The motor nerve conduction velocity was markedly decreased in MMT-treated mice. The Na(+),K(+)-ATPase activity of sciatic nerve isolated from MMT-treated mice was decreased; however, the sciatic nerve Na(+),K(+)-ATPase activity was not affected by the in vitro treatment of MMT. Moreover, [(3)H]ouabain binding of sciatic nerve isolated from MMT-treated mice was decreased. Using Western blot analysis, the amount of Na(+),K(+)-ATPase catalytic alpha1 subunit polypeptide in sciatic nerve of MMT-treated mice was also decreased. These results indicate that a causal relationship may exist between reduced nerve Na(+),K(+)-ATPase activity and motor nerve conduction velocity in MMT-treated mice and that a measurable decrease in alpha1 catalytic subunit isoform of Na(+),K(+)-ATPase may be necessary for the development of peripheral neuropathy by MMT.