ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents.
ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents.
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DOI：
10.1152/jn.01011.2014
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发表时间：
2015-04
影响因子：
2.5
通讯作者：
H. Ferreira-Neto;V. Antunes;J. Stern
中科院分区：
文献类型：
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作者：
H. Ferreira-Neto;V. Antunes;J. Stern
我们以前已经表明，室旁核（PVN）内的ATP诱导交感神经活动的增加，P2和/或多巴胺能受体的拮抗作用减弱的效果。在这里，我们评估了精确的细胞机制的ATP-谷氨酸相互作用的PVN，并评估是否这种受体偶联有助于刺激驱动交感PVN神经元的活动。从PVN-头端延髓腹外侧神经元获得的全细胞膜片钳记录显示，ATP（100 μM，1 min，水浴应用）诱导放电频率增加（89%），犬尿烯酸（1 mM）或4-[[4-甲酰基-5-羟基-6-甲基-3-[（膦酰氧基）甲基]-2-吡啶基]偶氮]-1，3-苯二磺酸四磺酸盐（PPADS）（10 μM）可阻断该效应。而ATP不影响谷氨酸突触功能，α-氨基-3-羟基-5-甲基异恶唑丙酸（AMPA）受体介导的电流引起的局部应用AMPA（50 μM，n = 13）的幅度增加ATP（AMPA振幅：33%，AMPA面积：52%）。ATP增强AMPA电流被PPADS（n = 12）和胞内Ca（2+）螯合物（BAPTA，n = 10）阻断。最后，高渗刺激（甘露醇1%，+55 mosM，n = 8）增强诱发AMPA电流（53%），PPADS（n = 6）阻断该效应。两者合计，我们的数据支持P2和AMPA受体（可能的突触外位置）在PVN交感神经元，这是从事在响应于急性高渗刺激，这可能反过来有助于由PVN的交感神经兴奋性反应驱动的功能性刺激耦合。
We have previously shown that ATP within the paraventricular nucleus (PVN) induces an increase in sympathetic activity, an effect attenuated by the antagonism of P2 and/or glutamatergic receptors. Here, we evaluated precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN and assessed whether this receptor coupling contributed to osmotically driven sympathetic PVN neuronal activity. Whole-cell patch-clamp recordings obtained from PVN-rostral ventrolateral medulla neurons showed that ATP (100 μM, 1 min, bath applied) induced an increase in firing rate (89%), an effect blocked by kynurenic acid (1 mM) or 4-[[4-Formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS) (10 μM). Whereas ATP did not affect glutamate synaptic function, α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated currents evoked by focal application of AMPA (50 μM, n = 13) were increased in magnitude by ATP (AMPA amplitude: 33%, AMPA area: 52%). ATP potentiation of AMPA currents was blocked by PPADS (n = 12) and by chelation of intracellular Ca(2+) (BAPTA, n = 10). Finally, a hyperosmotic stimulus (mannitol 1%, +55 mosM, n = 8) potentiated evoked AMPA currents (53%), an effect blocked by PPADS (n = 6). Taken together, our data support a functional stimulatory coupling between P2 and AMPA receptors (likely of extrasynaptic location) in PVN sympathetic neurons, which is engaged in response to an acute hyperosmotic stimulus, which might contribute in turn to osmotically driven sympathoexcitatory responses by the PVN.