X-radiation actions on the neuromuscular transmission

The effects of high doses of X-radiation (100 kilorads) on the neuromuscular transmission of isolated sciatic nerve-sartorius muscle preparations of the frog, as evaluated by bioelectrical characteristics, were explored. Intracellular microelectrode recordings after X-irradiation showed that the resting, excitation and action potentials of nerve fibers approaching the synaptic terminal region of the motor end-plate became lessened, and also presented a slower velocity of impulse propagation, earlier than that observed in muscle cells. After forty minutes following the irradiation period, the neuromuscular transmission became blocked, although muscle fibers still responded to direct electrical stimulation. Records taken at the motor end-plate region of muscle cells, demonstrated the presence of postsynaptic miniature end-plate potentials (m.e.p.p.'s), the sequence of which fits closely into a random Poisson distribution. X-irradiation elicited an increase of the rate of m.e.p.p.'s and induced membrane changes over fine terminal nerve branches, leading into a failure to initiate and propagate action potentials. Only as time progressed, this nerve bioelectrical impairment was accompanied by a similar one in muscle cells, associated to the inability to develop contractile tension. The increase of m.e.p.p.'s frequency due to depolarization by a high K+ concentration, of presynaptic nerve membranes of control and irradiated preparations, was reversed by a high Mg+--Ca2+--free media. However, a concentration of Mg2+, which normally reduced quantal release of acetylcholine (ACh), without altering presynaptic nerve membrane potentials, failed to modify the spontaneous basal frequency of m.e.p.p.'s, both in irradiated and control preparations. The findings of the present study suggest that the presynaptic ACh synthesis, storage, and availability for ACh liberation are not early affected by X-rays, i.e. at a time when transmission from nerve to muscle had already failed. On the contrary, the most precocius membrane changes following X-irradiation, seem related to the mechanisms underlying nerve resting, excitation, and action potentials. The smallest presynaptic nerve terminal fibers close to the motor end-plate, are the most radiosensitive portion of the myoneural junction. Indeed, their bioelectric characteristics are early affected by X-rays, resulting in a failure to generate and propagate nerve impulses which lead to a blockade of neuromuscular transmission.