Fig. 7.

Model of differential frequency-dependent regulation of transmitter release by NO. The diagram of a cross section of a frog nmj depicts a PSC covering the nerve terminal facing a muscle fiber. A, Model of the tonic action of NO at the amphibian nmj, where we propose that the tonic production of NO originates from the muscle fibers. This NO modulates transmitter release via a cGMP-dependent pathway, whereas it may keep the sensitivity of PSCs for various neurotransmitters in a reduced state. The adenosine-induced depression is also regulated by the cGMP-dependent pathway that is consistent with the fact that this form of depression occurs during a low level of transmitter release.B, Proposed model of the activity-dependent production of NO by the PSCs. This would occur as a consequence of the activation of the PSCs during prolonged and repetitive stimulation that would trigger the release of Ca²⁺ from internal stores and the activation of the neuronal type of NOS present in PSCs. This NO would then be modulating the release of neurotransmitter in a cGMP-independent manner, perhaps via direct protein modification that would alter the availability of the synaptic vesicles for exocytosis or endocytosis. GC, Guanylate cyclase;mf, muscle fiber; nt, nerve terminal;SP, substance P.