Presynaptic effects of bekanamycin at the frog neuromuscular junction. Reversibility by calcium and aminopyridines

The effects of bekanamycin (5-320 microM) on evoked and spontaneous transmitter release were examined in frog neuromuscular junctions in vitro by using conventional electrophysiological techniques. Bekanamycin in a concentration-dependent fashion reduced reversibly the quantal content of the end-plate potentials while it had no observable effect on the configuration of the extracellularly recorded presynaptic action potential. The reduction in evoked transmitter release produced by bekanamycin could be antagonized either by increasing the external calcium concentration or by drugs like the aminopyridines which are to greatly enhance transmitter release from motor nerve terminals. Regarding the possible mode of action of bekanamycin on transmitter release our results are consistent with the hypothesis that there is competition between calcium and bekanamycin in the excitation-secretion coupling process and that the site of competition has a higher affinity for bekanamycin than for calcium. Bekanamycin also reduced in a dose-dependent manner the acceleration of miniature end-plate potentials induced by increasing the extracellular K+ concentration while it had no effect on spontaneous miniature end-plate potential frequency in resting junctions. Besides its inhibitory pre-junctional effects bekanamycin in concentrations higher than 40 microM decreased dose-dependently the amplitude of miniature end-plate potentials. However, presynaptic effect predominated and seemed to be quantitatively more important for the neuromuscular block than was a possible postsynaptic action of the Antibiotic. It is concluded that bekanamycin exerts potent inhibitory effects on transmitter release probably by interfering with the influx of calcium that occurs during depolarization of motor nerve terminals.