Uni-quantal endplate currents (EPC) were recorded at mouse diaphragm neuromuscular synapse by extracellular microelectrode during motor nerve stimulation. The probability of release expressed as quantal content mo, and variability of synaptic latencies expressed as P90
were estimated in the presence of extracellular calcium ([Ca2+]o)
varying between 0.2 and 0.6 mM in the bathing solution. At 0.2 mM [Ca2+]o, mo was low (0.10) and many of long-latency EPCs were present during the late phase of the release (P90 = 2.44 ms). No change in mo was found when [Ca2+]o was 0.3 mM, but P90
decreased by 39 %. For latency shortening, saturating concentration of [Ca2+]o was 0.4 mM, when P90 was 1.49 ms and latencies did not further change at 0.5 and 0.6 mM [Ca2+]o. In the latter concentrations, however, an increase of mo was still observed. It can be concluded that the early phase of the secretion did not significantly change when [Ca2+]o was raised and that only the late phase of the release depends on extracellular
calcium up to 0.4 mM.
A novel derivative of 6-methyluracil, C-547, increased the amplitude and prolonged the duration of miniature endplate currents (MEPCs) which is typical for acetylcholinesterase inhibition. In the soleus and extensor digitorum longus significant potentiation was detected at nanomolar concentrations. In contrast, in the diaphragm muscle, the increase in the amplitudes of the MEPCs and the decay time constant appeared only when the concentration of C-547 was elevated to 1x10-7 M. Possible consequences for the exploitation of this drug, which can selectively inhibit AChE in particular synapses, are discussed.