Consequences of axonal transport blockade by batrachotoxin on mammalian neuromuscular junction. II. Late pre- and...

The present study describes the time course of recovery in the fast axonal transport of 3H-labeled proteins in the nerve and the electrophysiological parameters in the extensor muscle of rats after single subperineural injection of batrachotoxin (BTX) (9.3 x 10(-12) mol) into the peroneal nerve. The fast axonal transport of 3H-labeled proteins in the sciatic nerve showed significant accumulation of the labeled proteins proximal to the site of BTX injection at day 2. However, by day 7, when no locomotor deficit was visible, complete recovery of fast axonal transport had occurred. The recovery of membrane potential in this surface fibers of the extensor muscle, which showed atrophy even after 22 days of toxin administration, lagged far behind the recovery in the fast axonal transport. Between day 2 and 14 the extensor muscle showed partial membrane depolarization with almost complete recovery by day 22. From 18 h to 7 days after subperineural BTX injection, spontaneous (m.e.p.p.s.) or nerve evoked transmitter release were absent at the endplates of the affected extensor muscles. M.e.p.p.s. of very low frequency began to appear between day 7 and 10. Even at days 14 and 22, when most of the fibers tested showed m.e.p.p.s, the frequency of these mepps was significantly lower than that shown in corresponding control muscles. The profile of sensitivity of the extrajunctional region to microiontophoretically applied acetylcholine (ACh) showed extensive sensitivity (about 200 mV/nC) up to 14 days after BTX injection when the extensor muscle membrane was considerably depolarized. However, at day 22, when the RMP had returned to the control level, neither extrajunctional supersensitivity to ACh nor TTX-resistant action potentials could be detected. The persistence of membrane depolarization and other denervation signs in the extensor muscle, despite recovery in the fast axonal transport, suggests the existence of a blockade of other key particulates delivered to the synaptic region by slow axonal transport. The time course of recovery in the extensor muscle after BTX injection resembles in many respects that seen after nerve crush injury. The rate of recovery is fast due mostly to the ability of the toxin to produce disorganization and to depolarize the nerve without producing a break in continuity of the cytoarchitecture of axon.