Nitric Oxide (NO) is a highly diffusible second messenger that is generated in the CNS by synaptic activity and Ca2+-dependent stimulation of neuronal nitric oxide synthase (nNOS). NO signalling modulates ion channels, intrinsic excitability and synaptic plasticity. In the light of its presence in the principal neurons of the medial nucleus of the trapezoid body (MNTB), we have investigated NO-mediated modulation of CaVs and small conductance K+ channels (SK) in mediating an afterhyperpolarization (AHP). Whole-cell patch recordings were made from brain slices from P13-15 CBA mice. Slices were incubated with the inhibitor of neuronal nitric oxide synthase (nNOS) 7-nitroindazole (10μM) and pharmacological blockers used to isolate different CaV currents. Unpaired observations in the presence and absence of the NO-donor sodium nitroprusside (SNP, 100μM) were made to elucidate NO-dependent modulation of Apamin sensitive AHPs. Previous investigations had revealed a NO induced potentiation of CaV1 and CaV2.1 channels (Tozer et al. 2012), and here we show that this increase in ICa underlies the potentiation of the Apamin sensitive ISK by NO. The potentiation of ISK was blocked by the P/Q-type antagonist ω-Agatoxin IVA (200nM). NO significantly enhanced AHP duration evoked following postsynaptic current injections which evoked AP trains of 400Hz, for 1s (control tau, 32.7±3.9ms (n=5); NO tau, 51.9±5.2ms (n=5, p<0.05)), and the enhanced AHP duration was blocked by 100nM Apamin (tau 35.1±3.6ms (n=4, p<0.05)) (mean±SEM, student’s t-test). AHPs generated following presynaptic calyceal stimulation at 400Hz (300ms duration) in the presence of NO were also blocked by Apamin. These data suggest that in addition to modulation of voltage-gated K+ Channels, NO also contributes to homeostatic control of excitability, by potentiation of voltage-gated calcium channels and modulation of an SK-mediated AHP.