Changes in nerve membrane polarization following repeated exposure to soman.
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.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D012999:Soman / Q000494:pharmacology*
D000631:Aminopyridines; D007473:Ion Channels; D010042:Ouabain; D012999:Soman; D015761:4-Aminopyridine; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium