Characteristics of slow-miniature endplate currents show a subunit composition

Abstract

The normal neuromuscular junction shows two classes of spontaneous miniature endplate potentials. These classes are based on a discontinuity in the profile of miniature endplate potential amplitude distributions. The amplitude of one class of miniature endplate potentials from a bell-shaped amplitude distribution and the remaining miniature endplate potentials compose a population which forms a left-hand skew distribution with a mode1/7 to1/10 that of the bell-miniature endplate potentials [Kriebel M. E. and Gross C. E. (1974) J. gen. Physiol. 64, 85–103]. Some skew-miniature endplate potentials have a slow time-to-peak and show breaks on the rising phase. Most treatments that alter the miniature endplate potential frequency change the ratio of skew-miniature endplate potentials/bell-miniature endplate potentials [Kriebel M. E. et al. (1976) J. Physiol. 262, 553–581]. The time characteristics of miniature endplate currents were readily altered in the isolated frog and mouse neuromuscular junctions with several agents known to increase the percentage of slow-miniature endplate potentials (heat, botulinum toxin, 4-aminoquinoline and increases in bath osmolarity). The slow-miniature endplate potential amplitudes were a continuum of amplitudes from skew- to giant miniature endplate potentials. The rising phases of miniature endplate potentials were a continuum from smooth to many with breaks and offsets. In a series of sequentially recorded slow-miniature endplate currents, many had congruent rising phases of constant slope regardless of amplitude or of time-to-peak. The rising phases of congruent slow-miniature endplate currents which showed a change in slope deviated at similar amplitudes. The least value of the slope of a slow-miniature endplate current was that of the sub-miniature endplate current; and, miniature endplate currents with overall lower slope values showed a wave pattern and/or irregular breaks which suggests summation of sequentially delayed sub-miniature endplate currents. Plots of the amplitude vs time-to-peak of miniature endplate currents from identified junctions demonstrated that the normal percentage of slow-miniature endplate currents was greatly increased with the treatments used here and that the time-to-peak of giant miniature endplate currents usually was longer than that of normally occurring bell-miniature endplate currents. Giant miniature endplate currents with short time-to-peak values are probably from two miniature endplate currents occurring, by chance, almost simultaneously. During and/or after treatments, miniature endplate currents formed clusters of similar size miniature endplate currents, not randomly distributed in time, which graded from distinct miniature endplate currents to giant miniature endplate currents. Slow-miniature endplate currents with and without breaks on their rising phases were simulated with a computer using subunits that were combined by various numbers at various rates. Computer-generated miniature endplate currents simulate with fidelity the complete range of normal and treatment-induced slow-miniature endplate currents. We conclude that most slow-miniature endplate currents ranging in size from skew- to giant miniature endplate currents are fast bursts of dependent miniature endplate currents of the skew class, and that the treatments used here act in a non-specific manner to increase slow-miniature endplate currents.