HIGH PERCENTAGE OF SKEW-DISTRIBUTED MINIATURE END-PLATE CURRENTS IN OLD MICE

Muscle fibers from diaphragms of old (14 to 24 months) and young adult (I to 2 months) inbred (strain C57BL/6) mice were voltage clamped at - 140 mV with two microelectrodes near the neuromuscular junction. Min iature endplate currents (MEPCs) were digitized so that peak amplitude s and rise times could be determined. MEPC amplitude distributions fro m 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 di stributions 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 mod e, and some (20%) showed two peaks, representing both skew- and bell-M EPC classes. MEPC rise-time distributions from old mice varied between fibers, although they all had similar modes. Some (30%) were bell sha ped (similar to those in young mice) with a mode between 0.5 and 1 ms (coefficient of variation, 40%), but most distributions were skewed. E ndplates with smaller mean MEPC amplitudes showed a longer mean rise t ime, and for a given junction, MEPC amplitudes were correlated positiv ely to the corresponding rise times. This observation, together with a nalyses of the rising phases, indicates that MEPCs with long rise time s were not generated at remote sites. We discuss our results with rega rd to the hypothesis of a dynamic formation of transmitter packets, an d we attribute long rise time, skew-MEPCs to a prolonged release proce ss. During aging, the state of release that generates the skew-MEPC cl ass appears more dominant than the state generating the bell-MEPC clas s.