The presynaptic modulation of corticostriatal afferents by μ-opioids is mediated by K+ conductances

The presynaptic modulation of corticostriatal afferents by μ-opioids is mediated by K+ conductances
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DOI:
10.1016/s0014-2999(02)02877-7
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发表时间:
2003-02-21
影响因子:
5
通讯作者:
Bargas, J
Bargas, J
中科院分区:
医学2区
文献类型:
--
作者:
Barral, J;Mendoza, E;Bargas, J

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使用与成对脉冲比方案相关的种群峰值来测量由mu-阿片受体激活引起的皮质纹状体传递的突触前抑制。选择性阿片受体激动剂[D-Ala(2), N-MePhe(4), Gly-ol(5)-enkephalin (DAMGO)]的1mum可使配对脉冲促进率提高44 +/- 8%。这种作用被2 nM的选择性mu受体拮抗剂d - ph - cys - tyr - d - trp - orri - thr - nh (CTOP)完全阻断。n和P/ q型Ca2+通道拮抗剂抑制突触传递,而钾通道拮抗剂增强突触传递。1 μ m ω -谷草毒素GVIA (n型Ca2+通道阻滞剂)对DAMGO的作用没有影响,但400 μ m ω -谷草毒素TK (P/ q型Ca2+通道阻滞剂)部分阻断了DAMGO的作用。然而,5mmcs2 +和400mmba2 +的非选择性钾电导拮抗剂完全阻止了DAMGO对皮质纹状体传导的作用。这些数据表明,mu-阿片样物质对皮质纹状体传入事件的突触前抑制是通过皮质纹状体传入事件中K+电导的调节介导的。(C) 2002 Elsevier Science B.V.版权所有
Population spikes associated with the paired pulse ratio protocol were used to measure the presynaptic inhibition of corticostriatal transmission caused by mu-opioid receptor activation. A 1 muM of [D-Ala(2), N-MePhe(4), Gly-ol(5)-enkephalin (DAMGO), a selective [mu-opioid receptor agonist, enhanced paired pulse facilitation by 44 +/- 8%. This effect was completely blocked by 2 nM of the selective mu-receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orri-Thr-NH (CTOP). Antagonists of N-and P/Q-type Ca2+ channels inhibited, whereas antagonists of potassium channels enhanced, synaptic transmission. A 1 muM of omega-conotoxin GVIA, a blocker of N-type Ca2+ channels, had no effect on the action of DAMGO, but 400 nM omega-agatoxin TK, a blocker of P/Q-type Ca2+ channels, partially blocked the action of this opioid. However, 5 mM CS2+ and 400 muM Ba2+ unselective antagonists of potassium conductances, completely prevented the action of DAMGO on corticostriatal transmission. These data suggest that presynaptic inhibition of corticostriatal afferents by mu-opioids is mediated by the modulation of K+ conductances in corticostriatal afferents. (C) 2002 Elsevier Science B.V. All rights reserved.