| Annotated protein: | Nitric oxide synthase 1 (EC 1.14.13.39) (Constitutive NOS) (NC-NOS) (NOS type I) (Neuronal NOS) (N-NOS) (nNOS) (Nitric oxide synthase, brain) (bNOS) (Peptidyl-cysteine S-nitrosylase NOS1). Gene symbol: NOS1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9Z0J4 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NOS1 |
| Ontology domain: | Biological Process |
| SynGO term: | synaptic signaling by nitric oxide (GO:0099163) |
| Synapse type(s): | Calyx of Held |
| Annotated paper: | Steinert JR, et al. "Nitric oxide is a volume transmitter regulating postsynaptic excitability at a glutamatergic synapse" Neuron. 2008 Nov 26;60(4):642-56 PMID:19038221 |
| Figure(s): | Fig. 5 and Fig. 8. |
| Annotation description: | Fig 5, in the calyx of Hell synapses NO Reduces Synaptic Strength by Depressing Postsynaptic AMPAR and NMDAR Literal: "Patch-clamp recordings from innervated MNTB neurons exhibited calyceal EPSCs with a mean amplitude of 7.9 nA at the holding potential of -60 mV. NO donors (SNP, 100 mM or DEA, 100 mM) suppressed the evoked AMPAR-mediated EPSCs by 35% ± 4% (n = 7) and slowed the decay kinetics from 0.37 ± 0.07 ms to 0.86 ± 0.2 ms (HP = -60 mV, 37C, Figures 5A-5D). Similar observations were made for NMDAR-mediated currents with a mean amplitude of 1.8 nA (HP = +50 mV, Figures 5B-5D). The inhibition of both the AMPAR- and NMDAR-mediated EPSCs was mimicked by an SSP, and this was blocked by perfusion with the nNOS antagonist 1400W (10 mM). Although some of these changes could be mediated by either presynaptic or postsynaptic mechanisms, examination of spontaneous miniature EPSCs (mEPSC) in MNTB neurons clearly shows a postsynaptic mechanism. NO donors had no significant effect on release probability, since mEPSC frequencies were unchanged on perfusion of SNP (fcontrol = 7.0 ± 2.9 Hz; fNO = 6.6 ± 3.8 Hz, n = 5). But mEPSC amplitudes were reduced by 27.2% ± 2.3% and their decay kinetics slowed to a similar extent as for evoked EPSCs (mEPSCControl = -73.7 ± 4.8 pA; mEPSCNO = -53.7 ± 4.2 pA; tControl = 0.34 ± 0.02 ms; tNO = 0.51 ± 0.01 ms; HP = -60 mV, p < 0.05, paired Student's t test, n = 5; Figures 5E and 5F). Data from the same neuron showed identical changes for evoked EPSCs and mEPSCs on SNP application (inset, Figure 5E). Mean data show comparable significant changes (inset, Figure 5F) and in a further three cases synaptic stimulation with an SSP caused a similar 34.9% ± 11.3% reduction in mEPSC amplitudes. The equivalent depression of amplitude and slowed time course for both miniature and evoked EPSCs is incompatible with a presynaptic mechanism but is consistent with a postsynaptic modulation of AMPAR and NMDAR and is similar to that reported for AMPAR in the hippocampus (Lei et al., 2000). These results confirm that NO has multiple postsynaptic sites of modulatory action: it suppresses postsynaptic Kv3 potassium channels and reduces and slows the evoked calyceal EPSC. Fig. 8, activity-dependent changes in the calyx of Hell synapses are absent in NOS1 KO mouse Literal: "Whole-cell patch recordings were made from five MNTB neurons receiving calyceal inputs in brain slices from the KN2 mouse (Gyurko et al., 2002). The synaptic inputs were of similar magnitude to control animals (10.9 ± 1.1 nA, -60 mV, n = 5, data not shown). Outward potassium currents were also of similar magnitude to normal animals (Figure 8A, open triangles) and were sensitive to 3 mM TEA (data not shown). The outward current was unaffected by delivery of a SSP (open squares), and no change was observed in AP half-width following a SSP (Figure 8B). Furthermore, delivery of short synaptic trains (300 Hz, 150 ms) always generated postsynaptic APs, and this too was unaffected by a prior SSP (Figure 8C). In one case, application of an NO-donor after a negative SSP response, suppressed outward K+ currents, EPSCs, and broaden AP half-width, confirming that downstream components of the signaling pathway were otherwise intact in the KO animal." 8/11/2017 Pim - In this paper, NO (produced by nNOS) is shown to act as a volumentransmitter released from postsynapses to influcence the properties of ion channels localized in the postsynapse of neighboring synapses. Presynaptic changes in SV release could not be observed. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp |
| Annotator(s): | Chiara Verpelli (ORCID:0000-0003-2949-9725) Carlo Sala (ORCID:0000-0003-0662-9523) |
| Lab: | CNR Neuroscience Institute Milan and Dept. of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy |
| SynGO annotation ID: | 1803 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |