Electrophysiological investigation of 2,5-hexanedione neurotoxicity in rats

Rats were subcutaneously administered 0.8 ml/kg/day 2,5-hexanedione for periods of 18, 25, and 32 days, respectively, and were processed for electrophysiological observations. Action potential and membrane currents were recorded from the sciatic nerve under current- and voltage-clamp conditions. The contractile responses of gastrocnemius and diaphragm muscles following sciatic nerve and phrenic nerve stimulation, respectively, were observed. Animals developing peripheral neuropathy showed hindlimb weakness and depression of body weight gain. Current- and voltage-clamp experiments have shown that after 32 days treatment, the amplitude of the action potential recorded from single myelinated nerve fibers was reduced and the duration was slightly increased; peak sodium current was reduced by 15% and high potassium current density (12 nA) appeared. The twitch responses of diaphragm and gastrocnemius muscles following electrical stimulation of the phrenic and sciatic nerves, respectively, were strongly affected in the 32 day-treated rats. The results are discussed in terms of demyelination which should increase the amplitude of delayed current by exposing potassium channels which under physiological conditions are buried under the myelin sheath.