Powering of bulk transport (varicosities) and differential sensitivities of directional transport in growing axons

Abstract

Goldfish retinal ganglion cell (RGC) axons, regenerating in vitro, have varicosities, intervening phase-dense inclusions (IPDIs) and particles that are mobile. Varicosities contain an aggregate complex of cytomembranes embedded in a cytoskeletal matrix, and, when they saltate, they represent a form of bulk transport. While movement of varicosities is normally infrequent, the incidence of movement can be greatly increased by alkalinization with NH 4Cl. However, alkalinization also lowers the phase density of varicosities to reveal that motile hyperdense particles appear to be responsible for powering the translocation of varicosities and IPDIs. Other effects of alkalinization include a selective arrest of all anterograde movements and approximately a 10-fold reduction in the rate of retrograde mobility of particles and IPDIs. In mildly permeabilized axons, 20 μM orthovanadate selectively arrests retrogradely directed particle movements, while 100 μM arrests both antero- and retrograde transport. In addition to demonstrating in RGC axons that antero- and retrograde mechanisms exhibit differential pharmacological and pH sensitivities, the observations indicate that a heterogenous bulk mass can be translocated in growing axons by a passive ‘piggyback’ mechanism.