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In experiments with mouse diaphragm muscle, the effects of a nitric oxide (NO) donor, S-nitroso- N-acetyl-DL-penicillamine (SNAP), and an NO-synthase blocker, NG-nitro-L-arginine methyl ester (LNAME), on transmitter release and processes of exo- and endocytosis of synaptic vesicles in the motornerve ending were studied using electrophysiological and fluorescence techniques. During single stimulation of the motor nerve, SNAP reduced and LNAME did not change the amplitude of the endplate currents and both of the drugs did not affect spontaneous transmitter release. During high-frequency stimulation (20 Hz, 3 min) SNAP increased and LNAME slowed the depression of the amplitudes of endplate potentials (EPPs) compared to the dynamics of EPPs in the control. In experiments using the fluorescent dye FM 1–43, it was shown that the NO donor induced a decrease and LNAME induced an increase in the fluorescence intensity of motor-nerve endings loaded with dye during stimulation at a frequency of 20 Hz for 30 s compared to the control. At the same time, the rate of dye unloading from the terminals that were preloaded with FM 1–43 was higher after preliminary application of SNAP and lower after preliminary application of LNAME. It was suggested that exogenous and endogenous NO in the mouse neuromuscular synapse caused the depression of neurotransmitter release as a result of the suppression of synaptic-vesicle recycling due to a decrease in endocytosis or/and mobilization of synaptic vesicles from a recycling pool to the exocytosis sites.

An extracellular microelectrode applied to the neuromuscular junction of the frog sternocutaneus muscle was used to study effects of saturated (myristic and arachidic) and unsaturated (arachidonic and oleic) fatty acids on transmitter release and potassium currents in a nerve ending. All these fatty acids decreased evoked transmitter release. Unsaturated fatty acids decreased the amplitude of voltage-dependent and calciumactivated potassium currents in a nerve ending, whereas saturated acids were ineffective. Rhythmic stimulation applied in the presence of arachidonic and oleic acids induced more pronounced facilitation of the transmitter release, whereas the effects of myristic and arachidic acids did not differ from control values. Deoxycholate was not able to reproduce the effects of fatty acids on the transmitter release and potassium current in a nerve ending. It was concluded that fatty acids can modulate transmitter release and synaptic excitatory transmission; these effects can have a significant influence on molecular mechanisms of exocytosis of synaptic vesicles and electrogenesis in a motor nerve ending. The latter effect is characteristic of unsaturated (arachidonic and oleic) acids, whereas the former effect does not depend on the degree of unsaturation at all.