The effect of the nitrix oxide (NO) pathway on voltage-dependent potassium currents in rat vestibular nuclear neurons was investigated by using the whole cell patch clamp technique. When cells were held at -70 mV and depolarized from -60 mV to + 40 mV in 10 mV increments, sustained outward potassium currents were evoked. The outward potassium currents were decreased by the addition of 10 microM sodium nitroprusside (SNP). And 1 mM 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) produced a similar effects to those of 10 microM SNP. High EGTA containing pipette solution (11 mM) reduced the control currents and inhibited SNP induced outward potassium currents reduction. 1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ), a specific inhibitor of soluble guanylyl cyclase, significantly blocked SNP induced reduction. These results suggest that nitric oxide blocks Ca2+-activated K+ channels in the medial vestibular nuclear neuron by activating guanylyl cyclase.