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The nitric oxide (NO)/cyclic GMP signaling pathway has been suggested to be important in the formation of olfactory memory in insects. However, the molecular targets of the NO signaling cascade in the central neurons associated with olfactory learning and memory have not been fully analyzed. In this study, we investigated the effects of NO donors on single voltage-dependent Na +  channels in intrinsic neurons, called Kenyon cells, in the mushroom bodies in the brain of the cricket. Step depolarization on cell-attached patch membranes induces single-channel currents with fast-activating and -inactivating brief openings at the beginning of the voltage steps followed by more persistently recurring brief openings all along the 150-ms pulses. Application of the NO donor S-nitrosoglutathione (GSNO) increased the number of channel openings of both types of single Na +  channels. This excitatory effect of GSNO on the activity of these Na +  channels was diminished by KT5823, an inhibitor of protein kinase G (PKG), indicating an involvement of PKG in the downstream pathway of NO. Application of KT5823 alone decreased the activity of the persistent Na +  channels without significant effects on the fast-inactivating Na +  channels. The membrane-permeable cGMP analog 8Br-cGMP increased the number of channel openings of both types of single Na +  channels, similar to the action of NO. Taken together, these results indicate that NO acts as a critical modulator of both fast-inactivating and persistent Na +  channels and that persistent Na +  channels are constantly upregulated by the endogenous cGMP/PKG signaling cascade.    NEW &amp; NOTEWORTHY This study clarified that nitric oxide (NO) increases the activity of both fast-inactivating and persistent Na +  channels via the cGMP/PKG signaling cascade in cricket Kenyon cells. The persistent Na +  channels are also found to be upregulated constantly by endogenous cGMP/PKG signaling. On the basis of the present results and the results of previous studies, we propose a hypothetical model explaining NO production and NO-dependent memory formation in cricket large Kenyon cells.

journal of neurophysiology

Nitric oxide augments single persistent Na<sup>+</sup>channel currents via the cGMP/PKG signaling pathway in Kenyon cells isolated from cricket mushroom bodies

Nitric oxide augments single persistent Na+channel currents via the cGMP/PKG signaling pathway in Kenyon cells isolated from cricket mushroom bodies

Nitric oxide augments single persistent Na⁺channel currents via the cGMP/PKG signaling pathway in Kenyon cells isolated from cricket mushroom bodies