Inflammatory bowel diseases (IBD) are associated with altered neuronal regulation of the gastrointestinal (GI) tract and impairment of noradrenaline release from sympathetic varicosities. The sympathetic innervation of the GI tract modulates motility, blood flow and secretion and therefore, defective noradrenaline release may contribute to symptom generation in IBD. Accordingly, our aim here was to utilise the mouse model of dextran sulphate sodium (DSS; 5% wt/vol) of IBD to determine how noradrenaline release is reduced during GI inflammation. We hypothesised that the inflammation-induced reduction in noradrenaline release was due to inhibition of voltage-gated Ca²⁺ current (I_Ca) in prevertebral sympathetic neurons. We compared H³-noradrenaline release in the colon and jejunum, and I_Ca amplitude in superior mesenteric ganglion (SMG) neurons from control mice and mice with DSS-induced colitis. Changes to voltage-gated Ca²⁺ channels were investigated using Fura-2 AM Ca²⁺ imaging, perforated patch clamp electrophysiology and real time PCR. Depolarisation-induced noradrenaline release from the inflamed colon and uninflamed jejunum was significantly impaired in mice treated with DSS, as was depolarisation-induced Ca²⁺ influx in SMG neurons. Colitis reduced I_Ca in SMG neurons by inhibiting -conotoxin GVIA (300 nM)-sensitive N-type Ca²⁺ channels. The -conotoxin GVIA-sensitive component of noradrenaline release was significantly smaller in the colon during colitis. The inhibition of I_Ca was accompanied by a decrease in mRNA encoding the Ca²⁺ channel alpha subunit (CaV 2.2) and a rightward shift in the voltage-dependence of activation of I_Ca. These findings suggest that DSS-induced colitis attenuates noradrenaline release in the colon and jejunum due to inhibition of N-type voltage-gated Ca²⁺ channels. This may contribute to functional alterations in both inflamed and uninflamed regions of the GI tract during inflammation.