Consequences of axonal transport blockade induced by batrachotoxin on mammalian neuromuscular junction I. Early pre- and postsynaptic changes.

Subperineural injections of batrachotoxin (BTX) (1.86 X 10-12 or 9.3 X 10-12 mol) were made into the peroneal nerve at 10-12 or 33-35 mm from the entrance of the nerve into the extensor muscle of the rats. Measurements of fast axonal transport in the nerve and the resting membrane potential (RMP) from the surface fibers of the extensor muscle were made at intervals up to 18 h after injection of the toxin. The transport of 3H-labeled proteins and nerve conduction were blocked almost instantaneously by either dose of toxin. At 18 h some radioactive material distal to the BTX injection site could be seen, indicating partial recovery in fast axonal transport. Membrane depolarization of about 4 mV was evident in the surface fibers of the extensor muscle 50 min after injecting BTX in the peroneal nerve at a distance of 10 mm from the muscle. If the toxin was injected into the nerve at a farther site (33-35 mm), the onset of muscle membrane depolarization occurred at 120 min. The muscle membrane depolarization seen after injection of BTX at these two sites in the nerve was not a result of the toxin acting directly on the muscle nor was the depolarization reversibly by bath applied tetrodotoxin (TTX). Similar subperineural injections of TTX (6.3 X 10-9 mol) into peroneal nerve failed to cause any membrane depolarization in the extensor muscle even up to 18 h although the leg on the injected side was paralyzed in the same fashion as was the one with BTX. Membrane potential consistently recovered at 18 h in all BTX-injected animals although spontaneous release of transmitter had completely ceased at this time. These results conclusively demonstrate the fact that blockade of axonal transport by BTX and not suppression of electrical activity in the nerve caused by this agent is responsible for the early membrane depolarization of surface fibers of the extensor muscle. Thus the notion that resting membrane potential is under neurotrophic control is further supported. Muscle inactivity produced by paralysis of the affected limb alone apparently plays very little role in the onset of muscle depolarization and cessation of transmitter release.