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Changes in nerve membrane polarization following repeated exposure to soman
R J Anderson1, W L Chamberlain
1Department of Pharmacology, Warner-Lambert/Parke-Davis, Ann Arbor, Michigan.
Abstract:
The purpose of this study was to determine whether the slowly developing changes in potassium-induced depolarization in nerve membrane produced by soman are due to blockade of potassium conductance or to inhibition of Na,K-ATPase. Rats were dosed daily for 20 d with soman (0.075 mg/kg, ip). In isolated sucrose gap chambers, the nerves were challenged with extracellular potassium in the presence and absence of ouabain, 4-aminopyridine, and ouabain plus 4-aminopyridine. The enhancement of potassium-induced depolarization produced individually by ouabain and 4-aminopyridine was unaffected by soman pretreatment of the nerves. However, in the presence of both ouabain and 4-aminopyridine the soman-treated nerves showed a marked enhancement of potassium-induced depolarization. This effect was not seen in nerves exposed to soman for only 1 d. These results show that soman affects a nerve-membrane process other than potassium channels or Na,K-ATPase. The role of this unidentified process apparently is important in maintaining nerve function only when potassium conductance is blocked and Na,K-ATPase is inhibited. Furthermore, the effect of soman on this process is the result of an adaptive change rather than a direct effect, since single-dose exposure produced no shift in potassium-induced depolarization.