Articles in PresS . J Neurophysiol ( April 23 , 2003 ) . 10 . 1152 / jn . 00225 . 2003

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 pavocellular neurons (n = 243) were depolarized by 100 nM NMU, but magnocellular neurons were not affected. NMU (10 nM to 1 μM) 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 μM tetrodotoxin (TTX) + 10 μM CNQX + 10 μM bicuculline. Extracellular application of 70 μM ZD 7288 completely inhibited NMU-induced depolarization. Under voltage-clamp, 1 μM NMU produced negligible inward current but did increase the hyperpolarization-activated current (IH) at step potentials less than –80 mV. The effects of NMU on IH were voltage-dependent, and NMU shifted the IH conductance-voltage relationship (V1/2) by about 10.8 mV and enhanced IH kinetics without changing the slope constant (k). Extracellular application of 70 μM ZD 7288 or 3 mM Cs blocked IH and the effects of NMU in voltage-clamp. These results suggest that NMU selectively depolarizes the subpopulation of PVN pavocellular neurons via enhancement of the hyperpolarization-activated inward current.