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

The in gigo 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, [³H]ouabain binding of sciatic nerve isolated from MMT-treated mice was decreased. Using Western blot analysis, the amount of Na⁺,K⁺-ATPase catalytic α1 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 α1 catalytic subunit isoform of Na⁺,K⁺-ATPase may be necessary for the development of peripheral neuropathy by MMT. (C) 2000 Academic Press.