Endogenous nitric oxide but not exogenous no-donor S-nitroprussiate facilitates NMDA excitation in spontaneous rhythmic neonatal rat brainstem slice

Abstract

Nitric oxide (NO) is an excitatory agent within the isolated respiratory network of immature rats (Pierrefiche et al., 2002) and modulates bursting discharge of rhythmic respiratory neurone in juvenile rats (Pierrefiche et al., 2007). However, whether NO is acting directly via a specific cellular mechanism or by increasing NMDA receptor activity is unknown. Our present aim was to study NO modulation of NMDA-induced excitation within the isolated neonatal respiratory network. The NO-scavenger, haemoglobin, and the NOS inhibitor l-NO-Arg, reduced spontaneous activity and were more effective during NMDA-induced excitation. Both diethylamine-NO (DEA-NO) and S-nitroprussiate (SNP), two NO-donors not related chemically, increased spontaneous activity in a dose-dependent manner. However, when co-applied with NMDA only DEA-NO facilitated NMDA-induced excitation whereas SNP partially reversed or prevented NMDA-induced excitation. Similar reversion of NMDA-induced excitation were obtained with K3–(FeCN)6 (Fe III) or inactivated SNP. On the contrary, FeSO4 did not have any effect on either spontaneous activity or NMDA-induced excitation. These data suggest that activation of NMDA receptors increase endogenous NO production which participates in endogenous NMDA-induced excitation during spontaneous XII bursting activity. It also demonstrated that the type of NO-donors used during pharmacological study implicating NMDA receptors should be carefully chosen.