Neuromedin U depolarizes rat hypothalamic paraventricular nucleus neurons in vitro by enhancing IH channel activity.

Neuromedin U depolarizes rat hypothalamic paraventricular nucleus neurons in vitro by enhancing IH channel activity.
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DOI:
10.1152/jn.00225.2003
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发表时间:
2003-08
影响因子:
2.5
通讯作者:
De-Lai Qiu;Chunping Chu;T. Shirasaka;Takashi Nabekura;T. Kunitake;Kazuo Kato;M. Nakazato;T. Katoh;H. Kannan
De-Lai Qiu;Chunping Chu;T. Shirasaka;Takashi Nabekura;T. Kunitake;Kazuo Kato;M. Nakazato;T. Katoh;H. Kannan
中科院分区:
医学3区
文献类型:
--
作者:
De-Lai Qiu;Chunping Chu;T. Shirasaka;Takashi Nabekura;T. Kunitake;Kazuo Kato;M. Nakazato;T. Katoh;H. Kannan

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采用全细胞膜片钳技术观察神经介素U(NMU)对大鼠室旁核(PVN)神经元的影响。在电流钳下,31%的PVN小细胞神经元(n = 243)被100 nM NMU去极化,但大细胞神经元不受影响。NMU(10 nM至1 μ M)以剂量依赖性方式导致基础放电率和去极化增加,EC 50为70 nM。用0.5 μ M TTX + 10 μ M 6-氰基-7-硝基喹喔啉-2,3-二酮(CNQX)+ 10 μ M荷包牡丹碱共灌注不影响NMU诱导的去极化。细胞外应用70 μ M ZD 7288完全抑制了NMU诱导的去极化。在电压钳下,1 μ M NMU产生的内向电流可忽略不计,但在阶跃电位小于-80 mV时确实增加了超极化激活电流(IH)。NMU对IH的影响具有电压依赖性,NMU使IH电导-电压关系(V1/2)偏移约10.8 mV,并增强IH动力学而不改变斜率常数(k)。细胞外应用70 μ M ZD 7288或3 mM Cs+阻断IH和NMU在电压钳中的作用。这些结果表明,NMU通过增强超极化激活的内向电流选择性地使PVN小细胞神经元亚群去极化。
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.