Previous work has shown endogenous cholinergic activity facilitates both GABAergic and glycinergic neurotransmission to premotor cardiac vagal neurons. Exogenous application of nicotine increases the frequency of glycinergic and GABAergic inhibitory postsynaptic currents (IPSCs) and miniature IPSCs (mIPSCs) to cardiac vagal neurons. In this study we examined whether the nicotine evoked facilitation of GABAergic and glycinergic neurotransmission to cardiac vagal neurons is dependent or independent of activation of voltage dependent calcium channels. Nicotine evoked increases in GABAergic and glycinergic mIPSCs in cardiac vagal neurons which were blocked by the non-specific calcium channel antagonist cadmium (100 microM). Application of the L (Cav 1) type calcium channel antagonist nimodipine (10 microM) had no effect. However, the increase in both GABAergic and glycinergic mIPSCs elicited by nicotine was abolished by the P/Q (Cav 2.1) voltage gated calcium channel antagonist omega-agatoxin IVA (100 nM). Omega-conotoxin GVIA (1 microM), a specific blocker of N (Cav 2.2) type voltage gated calcium currents, inhibited the nicotine elicited augmentation of GABA and abolished the increase in glycine mIPSC frequency. This work demonstrates that the nicotine evoked facilitation of GABAergic and glycinergic neurotransmission to cardiac vagal neurons is dependent upon activation of P/Q (Cav 2.1) and N (Cav 2.2) type calcium channels.