Podda, Maria Vittoria and Marcocci, Maria Elena and Oggiano, Leonardo and D'Ascenzio, Marcello and Tolu, Eusebio and Palamara, Anna Teresa and Azzena, Gian Battista and Grassi, Claudio (2004) Nitric oxide increases the spontaneous firing rate of rat medial vestibular nucleus neurons in vitro via a cyclic GMP-mediated PKG-independent mechanism. European Journal of Neuroscience, Vol. 20 (8), p. 2124-2132. eISSN 1460-9568. Article.
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The effects of nitric oxide (NO) on the discharge rate of medial vestibular nucleus neurons (MVNn) were investigated in rat brainstem slices. The NO-donor sodium nitroprusside (SNP, 200 µM) caused a marked enhancement (+36.7%) of MVNn spontaneous firing rate, which was prevented by the NO-scavenger, carboxy-PTIO (300 µM). The SNP effects were not modified (+37.4%) by synaptic uncoupling, suggesting that NO influences intrinsic membrane properties of MVNn rather than the synaptic input they receive. The excitatory action of SNP was virtually abolished by slice pretreatment with the soluble guanylyl cyclase inhibitor, ODQ (10 µM), and it was mimicked (+33.1%) by the cGMP analogue 8-Br-cGMP (400 µM). Protein kinase G (PKG) and cAMP/protein kinase A (PKA) were both excluded as downstream effectors of the NO/cGMP-induced excitation. However, the cyclic nucleotide-gated (CNG) channel blockers, L-cis-diltiazem (LCD, 100 µM) and Sp-8-Br-PET-cGMPS (100 µM), significantly reduced the firing rate increase produced by 8-Br-cGMP. Moreover, LCD alone decreased spontaneous MVNn firing (−19.7%), suggesting that putative CNG channels may contribute to the tonic control of resting MVNn discharge. 8-Br-cAMP (1 mM) also elicited excitatory effects in MVNn (+40.8%), which occluded those induced by 8-Br-cGMP, indicating that the two nucleotides share a common target. Finally, nested-polymerase chain reaction assay revealed the expression of CNG channel α subunit transcript in MVNn. Our data provide the first demonstration that NO/cGMP signalling modulates MVNn spontaneous firing through a mechanism that is independent of PKG or PKA and probably involves activation of CNG channels.
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