Inhibition of the rapid movement of optically detectable axonal particles colchicine and vinblastine

The rapid saltatory motion of intra-axonal particles detected by dark-field microscopy in myelinated axons isolated from sciatic nerves of adult Xenopus laevis was inhibited by colchicine or vinblastine at a concentration of larger than or equal to 0.1 mM. Both the predominant somatopetal transport and the somatofugal transport of these round particles were inhibited. The reduction in numbers of moving particles was apparent first in the juxtanodal portions of the isolated axons within about 1 h. No particles could be detected moving by 3-5 h after application of the colchicine or vinblastine. During the phase of partial inhibition, those particles that were still progressing along the axon did so at apparently normal velocities while they were in motion, but remained stationary increasingly frequently and for progressively longer periods. Colchicine or vinblastine at a concentration of less than or equal to 10 micronM caused no observable inhibition within 4 h of application. Colchicine at a concentration of larger than or equal to 10 mM caused local accumulation of round particles, and vinblastine at a concentration of larger than or equal to 2.5 mM caused fragmentation of rod-shaped organelles, believed to be mitochondria. Electron microscopy of nerve fibers treated with 5 mM colchicine showed a progressive loss of microtubules from the axoplasm, such that approximately 70% of the microtubules had disappeared after 4h.