Fast axonal transport: effect of antimitotic drugs and inhibitors of energy metabolism on the rate and amount of transported protein in frog sciatic nerves.

Abstract

Mitosis inhibitors, drugs affecting the energy metabolism, heavy water, and ouabain were used to partially inhibit fast axonal transport in frog sciatic nerves. Effects on the rate and on the amount of pulse labeled protein could be separated. The pulse of labeled protein, released after a cold-block, rapidly reached a maximum height which indicated that the transport system was saturated in the nerve segment occupied by the pulse. Both the rate and the amount were reduced by the mitosis inhibitors colchicine, vinblastine, and griseofulvin. Colchicine had a differential effect and reduced the rate of material migrating in the advancing front of the pulse less than the rate of that moving in the peak. Preincubation at low temperature potentiated the effects of colchicine. Two inhibitors of energy metabolism, NaCN and IAA, reduced the amount of labeled material in the pulse. The slope of the pulse was markedly reduced and multiple peaks appeared. The distance covered by the migrating pulse was largely unaffected, but some retardation of late components might have occurred. In contrast, 2.4-DNP reduced the rate without any effects on the amount of migrating material. Heavy water uniformly reduced the rate of the migrating pulse, whereas the main effect of ouabain was a diminished amount and multiple peaks as with NaCN and IAA. All drugs were tested for their effects on the electrical activity of sciatic nerves. The compound action potential was not affected by the mitosis inhibitors and heavy water, but was depressed by the inhibitors of energy metabolism and abolished by ouabain. The results indicate that the effects of various transport inhibitory drugs can be differentiated if both the rate and the amount are considered.