Neuromedin U depolarizes rat hypothalamic paraventricular nucleus neurons in vitro by enhancing IH channel activity.
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 microM) 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 microM TTX + 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) + 10 microM bicuculline. Extracellular application of 70 microM ZD 7288 completely inhibited NMU-induced depolarization. Under voltage-clamp, 1 microM 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 microM 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 parvocellular neurons via enhancement of the hyperpolarization-activated inward current.[1]References
- Neuromedin U depolarizes rat hypothalamic paraventricular nucleus neurons in vitro by enhancing IH channel activity. Qiu, D.L., Chu, C.P., Shirasaka, T., Nabekura, T., Kunitake, T., Kato, K., Nakazato, M., Katoh, T., Kannan, H. J. Neurophysiol. (2003) [Pubmed]
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