Mechanisms of the facilitation of neurotransmitter secretion in strontium solutions

Experiments on frog neuromuscular synapses using extracellular microelectrode recording of endplate currents (EPC) and nerve ending (NE) responses were performed to study the mechanisms of facilitation of quantum secretion of acetylcholine on replacement of extracellular Ca ions with Sr ions. Solutions with a Ca ion concentration of 0.5 mM (calcium solutions) or a Sr ion concentration of 1 mM (strontium solutions) were used; the basal levels of neurotransmitter secretion (in conditions of low-frequency stimulation) were essentially identical. In calcium solutions, the drop in EPC facilitation on paired-pulse stimulation as the interimpulse interval was increased from 5 to 500 msec was described by the sum of three exponential components - the early, the first, and the second. In strontium solutions, facilitation was decreased as compared with the level in calcium solutions predominantly because of decreases in the early and first components. At the same time, EPC facilitation in conditions of rhythmic stimulation (10 or 50 impulses/sec) in strontium solution was significantly increased as compared with the level in calcium solutions. In strontium solutions in conditions of high-frequency stimulation at 50 impulses/sec, there was also a marked decrease in the amplitude of the third phase of the NE response, reflecting NE potassium currents. These data lead to the conclusion that the facilitation sites underlying the first and early components had lower affinities for Sr ions than for Ca ions. Increases in facilitation in strontium solutions in conditions of high-frequency rhythmic activity resulted from two mechanisms: more marked widening of the NE action potential and an increase in the divalent cation influx current due to weak activation of the Ca2+-dependent potassium current in the presence of Sr ions, as well as the slow dynamics of the removal of Sr ions from the NE axoplasm as compared with that in the presence of Ca ions.