The effect of neuromedin U (NMU) on rat paraventricular nucleus (PVN) neurons was examined using whole cell patch-clamp recordings. Under current-clamp, 31% of PVN parvocellular neurons (n = 243) were depolarized by 100 nM NMU, but magnocellular neurons were not affected. NMU (10 nM to 1 muM) resulted in increased basal firing rate and depolarization in a dose-dependent manner with an EC50 of 70 nM. NMU-induced depolarization was unaffected by co-perfusion with 0.5 muM TTX + 10 muM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) + 10 muM bicuculline. Extracellular application of 70 muM ZD 7288 completely inhibited NMU-induced depolarization. Under voltage-clamp, 1 muM NMU produced negligible inward current but did increase the hyperpolarization-activated current (I-H) at step potentials less than -80 mV. The effects of NMU on I-H were voltage-dependent, and NMU shifted the I-H conductance-voltage relationship (V-1/2) by about 10.8 mV and enhanced I-H kinetics without changing the slope constant (k). Extracellular application of 70 muM ZD 7288 or 3 mM Cs+ blocked I-H and the effects of NMU in voltage-clamp. These results suggest that NMU selectively depolarizes the subpopulation of PVN parvocellular neurons via enhancement of the hyperpolarization-activated inward current.