Increase of large intramembranous particles in the presynaptic active zone after administration of 4-aminopyridine.

The effects of 4-aminopyridine (4-AP, 1 mg/kg i.v.) on the distribution of intramembranous particles in spinal motoneuronal synapses was examined in anesthetized (pentobarbital sodium, 50 mg/kg, i.p.) rats by freeze-etching electron microscopy. The particles were classified according to their size into small (4.2--10.5 nm in diameter) and large (10.5--18.9 nm in diameter). The active zone of the presynaptic membrane was identified on the basis of ultrastructural criteria. The large intramembranous particles in both protoplasmic (PF) and external fracture faces (EF) were aggregated more densely in the active zone as compared with its surroundings both in the control and 4-AP-treated group (P less than 0.001). The density of large particles in the PF rose from 300/sq.micron under the influence of 4-AP (P less than 0.001). The increased frequency of vesicle attachment sites at the presynaptic membrane (from 115/sq.micron in barbiturized controls to 150/sq.micron in 4-AP treated animals) seemed to be positively correlated with the increasing density of large particles. Based on these findings it is suggested that the large intramembranous particles of the presynaptic membrane may participate in the control of calcium fluxes which are essential to the transmitter release by exocytosis.