Statistics of neuromuscular transmitter release in young and old mouse muscle.

1. It was reported previously that in limb muscles of old (27-30 months) CBF-1 mice, quantal content (m) of evoked transmitter release was increased compared to that in young (9-12 months) mice. In diaphragm muscles there was no change with age. The object of the present study was to determine whether the age-related increase in transmitter release was due to increase in the binomial parameter n or the parameter p. The analysis also involved consideration of goodness-of-fit between observed and expected binomial distribution of the data. 2. Spontaneous miniature end-plate potentials (m.e.p.p.s) and evoked end-plate potentials (e.p.p.s) were recorded with intracellular techniques from soleus and diaphragm muscles bathed in low-Ca high-Mg medium. The goodness-of-fit between the observed e.p.p amplitude distribution and that expected from a binomial distribution was evaluated by chi 2 test. 3. In different muscles and at different ages, the percentage of fibres with binomial e.p.p. distributions varied from 17 to 44%, even though in all fibres there was a similar proportionality between direct quantal content and the reciprocal of the square of the coefficient of variation of e.p.p. amplitudes. In addition, apparent graphical agreement between observed and theoretical binomial e.p.p. distributions was often not substantiated by the chi 2 criterion. 4. In soleus muscles from young mice, lowering the stimulus frequency from 10 to 0.5 Hz and shortening the train length from 250 to 100 pulses increased the prevalence of binomial e.p.p. distributions, but the same result was not obtained in diaphragm or soleus muscles from old mice. If the mean amplitude of groups of 10 e.p.p.s in any train showed any drift (greater than 10%) then that train was excluded from the results. Thus, in order to make valid age comparisons, only fibres with binomial e.p.p. distributions were analysed further. 5. There was no change with age in m, n or p in diaphragm muscles, but in soleus muscles from old animals a nearly 2-fold increase in n entirely accounted for the increase in m. 6. If, as proposed by others, n represents the number of release sites, then the ageing soleus neuromuscular junction may have increased numbers or length of active zones or associated membrane components.