High percentage of skew-distributed miniature endplate currents in old mice

Muscle fibers from diaphragms of old (14 to 24 months) and young adult (1 to 2 months) inbred (strain C57BL/6) mice were voltage clamped at -140 mV with two microelectrodes near the neuromuscular junction. Miniature endplate currents (MEPCs) were digitized so that peak amplitudes and rise times could be determined. MEPC amplitude distributions from old mice varied greatly between fibers from the same diaphragm, and the mean MEPC amplitude (2.1 +/- 0.83 nA, mean +/- SD) was smaller than in young mice (5.2 +/- 0.59 nA). In old mice, some (50%) amplitude distributions were bell shaped, composed of mainly bell-MEPCs with a 2- to 5-nA mode, whereas others (30%) were skewed with a 0.5- to 2-nA mode, and some (20%) showed two peaks, representing both skew- and bell-MEPC classes. MEPC rise-time distributions from old mice varied between fibers, although they all had similar modes. Some (30%) were bell shaped (similar to those in young mice) with a mode between 0.5 and 1 ms (coefficient of variation, 40%), but most distributions were skewed. Endplates with smaller mean MEPC amplitudes showed a longer mean rise time, and for a given junction, MEPC amplitudes were correlated positively to the corresponding rise times. This observation, together with analyses of the rising phases, indicates that MEPCs with long rise times were not generated at remote sites. We discuss our results with regard to the hypothesis of a dynamic formation of transmitter packets, and we attribute long rise time, skew-MEPCs to a prolonged release process. During aging, the state of release that generates the skew-MEPC class appears more dominant than the state generating the bell-MEPC class.