McQuiston A R, Petrozzino J J, Connor J A, Colmers W F
Department of Pharmacology, University of Alberta, Edmonton, Canada.
J Neurosci. 1996 Feb 15;16(4):1422-9. doi: 10.1523/JNEUROSCI.16-04-01422.1996.
Neuropeptide Y (NPY) is far more abundant in the dentate gyrus than elsewhere in the hippocampal formation, but it does not alter the synaptic excitation of dentate granule cells (DGCs) as it does for pyramidal cells in areas CA1 and CA3. NPY inhibited depolarization-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in DGCs in hippocampal slices, without altering the resting [Ca2+]i. NPY inhibited Ca2+ currents (ICa) via a Y1 receptor in 84% of acutely isolated DGCs and via a Y2 receptor in 31% of the NPY-responsive cells tested. ICa inhibition was completely occluded by omega-conotoxin-GVIA but not by nimodipine. The inhibition of ICa was accompanied by a change in the time course of ICa activation in only 27% of NPY-responsive cells. Only 23% of DGCs responded to NPY when Ba2+ was substituted for extracellular Ca2+ and when [Ca2+]i was strongly buffered. Therefore, NPY inhibits an N-type ICa in DGCs, mainly via Y1 receptors. Furthermore, it seems that more than one mechanism, one of which may be sensitive to [Ca2+]i, may couple NPY receptors to the Ca2+ channels in DGCs. Because the release of dynorphin from DGCs depends in part on N-type currents, NPY receptors are poised to regulate the release of opioid peptides from DGC somata and dendrites.
神经肽Y（NPY）在齿状回中的含量远比海马结构的其他部位丰富，但它不像在CA1区和CA3区对锥体细胞那样改变齿状颗粒细胞（DGCs）的突触兴奋。NPY抑制海马切片中DGCs的去极化诱导的细胞内Ca2+浓度（[Ca2+]i）升高，而不改变静息[Ca2+]i。在84%的急性分离的DGCs中，NPY通过Y1受体抑制Ca2+电流（ICa），在31%的测试的NPY反应性细胞中通过Y2受体抑制ICa。ICa抑制完全被ω-芋螺毒素-GVIA阻断，但不被尼莫地平阻断。在仅27%的NPY反应性细胞中，ICa抑制伴随着ICa激活时间进程的改变。当用Ba2+替代细胞外Ca2+且[Ca2+]i被强烈缓冲时，只有23%的DGCs对NPY有反应。因此，NPY主要通过Y1受体抑制DGCs中的N型ICa。此外，似乎不止一种机制，其中一种可能对[Ca2+]i敏感，可将NPY受体与DGCs中的Ca2+通道偶联。因为DGCs中强啡肽的释放部分依赖于N型电流，NPY受体有望调节DGCs胞体和树突中阿片肽的释放。
