Is the quantum of transmitter release composed of subunits? A critical analysis in the mouse and frog

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Abstract
Miniature end-plate potentials (m.e.p.p.) were recorded from mouse diaphragm and frog cutaneous pectoris muscles and miniature end-plate currents (m.e.p.c.) were recorded from frog cutaneous pectoris to investigate whether the m.e.p.p. is built up of 1-30 subunits. The subunit theory is based on a class of m.e.p.p.s smaller than the classical m.e.p.p.s and histograms of m.e.p.p. amplitudes display multiple peaks which often appear regularly spaced and extend throughout the histograms. The subunit hypothesis predicts each successive peak results from an increasing integral number of subunits per m.e.p.p. (Kriebel Llados and Matteson Wernig and Stirner 1977.) Histograms of m.e.p.p. amplitudes and m.e.p.c. areas confirmed the 2 classes of m.e.p.p. as reported by Kriebel and Gross. A larger class (well described by a Gaussian curve) consisted of the classical m.e.p.p. and a smaller class had amplitudes considerably less than the classical m.e.p.p.s. Histograms of m.e.p.p. amplitudes and m.e.p.c. areas showed multiple peaks throughout the histograms. Autocorrelations of the histograms showed the multiple peaks were not regularly spaced, as required by the subunit hypothesis. A series of computer simulations were performed. For expected levels of base-line noise in the recording system, multiple peaks extending throughout histograms of m.e.p.p. amplitudes arose from subunits only if the SD of the subunit amplitude was less than 2-5% of the mean subunit amplitude and the SD of the variability in post-synaptic sensitivity was less than 2% of the mean post-synaptic sensitivity. The variability in post-synaptic sensitivity and proposed subunit amplitude does not seem this small. Realistic estimates for the SD of the subunit amplitude of 12% of the mean subunit amplitude and SD of the variation in post-synaptic sensitivity 4% the mean sensitivity, 3-4 regularly spaced peaks are apparent in m.e.p.p. amplitude histograms due to subunits. The multiple peaks observed to extend throughout histograms of m.e.p.p. amplitudes do not appear to arise from subunits. The multiple peaks observed to extend throughout m.e.p.p. amplitude histograms probably arise from random variation in the data.