SK3 介导的电流功能降低先于多巴胺能神经元中 AMPA 受体介导的兴奋性毒性。
Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons.
机构信息
Laboratory of Brain Development, Modulation and Repair, Brigham and Women's Hospital, Harvard Medical School, MA 02115, USA.
出版信息
Neuropharmacology. 2011 Jun;60(7-8):1176-86. doi: 10.1016/j.neuropharm.2010.10.024. Epub 2010 Oct 31.
Abstract
In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (I(SK)) in this system and evaluated their role on homeostasis against excitotoxicity. I(SK) amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of I(SK) for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two I(SK) agonists, 1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, I(SK) influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
摘要
在中脑的原代培养物中，小电导钙激活钾通道（SK）在多巴胺能神经元中表达。我们对该系统中的 SK 介导电流（I（SK））进行了表征，并评估了其在对抗兴奋性毒性方面的稳态作用。通过在膜中减少 SK 通道数量，谷氨酸能激动剂 AMPA 降低了 I（SK）的幅度。用 apamin 或 NS8593 阻断 I（SK）12 h 会以浓度依赖性方式减少多巴胺能神经元的数量。apamin 的作用与 AMPA 毒性不具有加性。另一方面，两种 I（SK）激动剂 1-EBIO 和 CyPPA 导致多巴胺能神经元自发丢失显著减少。1-EBIO 还逆转了 AMPA 和 apamin 的作用。因此，I（SK）影响多巴胺能神经元在体外的存活和分化，是保护性稳态反应的一部分，参与快速作用的负反馈回路，耦联钙水平、神经元兴奋性和细胞防御。本文是题为“神经药理学趋势：纪念 Erminio Costa”的特刊的一部分。
相似文献
1
Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons.SK3 介导的电流功能降低先于多巴胺能神经元中 AMPA 受体介导的兴奋性毒性。
Neuropharmacology. 2011 Jun;60(7-8):1176-86. doi: 10.1016/j.neuropharm.2010.10.024. Epub 2010 Oct 31.
2
Tuning the excitability of midbrain dopamine neurons by modulating the Ca2+ sensitivity of SK channels.通过调节小电导钙激活钾通道（SK通道）的钙敏感性来调节中脑多巴胺能神经元的兴奋性。
Eur J Neurosci. 2009 May;29(9):1883-95. doi: 10.1111/j.1460-9568.2009.06735.x. Epub 2009 Apr 20.
3
Age-dependent neuroprotective effect of an SK3 channel agonist on excitotoxity to dopaminergic neurons in organotypic culture.年龄依赖性 SK3 通道激动剂对器官型培养多巴胺能神经元兴奋性毒性的神经保护作用。
PLoS One. 2020 Jul 23;15(7):e0223633. doi: 10.1371/journal.pone.0223633. eCollection 2020.
4
Selective coupling of T-type calcium channels to SK potassium channels prevents intrinsic bursting in dopaminergic midbrain neurons.T型钙通道与SK钾通道的选择性偶联可防止多巴胺能中脑神经元的内在爆发。
J Neurosci. 2002 May 1;22(9):3404-13. doi: 10.1523/JNEUROSCI.22-09-03404.2002.
5
Differential expression of the small-conductance, calcium-activated potassium channel SK3 is critical for pacemaker control in dopaminergic midbrain neurons.小电导钙激活钾通道SK3的差异表达对多巴胺能中脑神经元的起搏器控制至关重要。
J Neurosci. 2001 May 15;21(10):3443-56. doi: 10.1523/JNEUROSCI.21-10-03443.2001.
6
Inhibitory gating modulation of small conductance Ca2+-activated K+ channels by the synthetic compound (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) reduces afterhyperpolarizing current in hippocampal CA1 neurons.合成化合物（R）-N-（苯并咪唑-2-基）-1,2,3,4-四氢-1-萘胺（NS8593）对小电导钙激活钾通道的抑制性门控调节可降低海马CA1神经元的超极化后电流。
Mol Pharmacol. 2006 Nov;70(5):1771-82. doi: 10.1124/mol.106.027110. Epub 2006 Aug 22.
7
SK Ca2+-activated K+ channel ligands alter the firing pattern of dopamine-containing neurons in vivo.SK 钙激活钾通道配体可改变体内含多巴胺神经元的放电模式。
Neuroscience. 2006 Jun 30;140(2):623-33. doi: 10.1016/j.neuroscience.2006.02.020. Epub 2006 Mar 29.
8
Small conductance calcium-activated potassium type 2 channels regulate alcohol-associated plasticity of glutamatergic synapses.小电导钙激活钾通道 2 型调节谷氨酸能突触的酒精相关可塑性。
Biol Psychiatry. 2011 Apr 1;69(7):625-32. doi: 10.1016/j.biopsych.2010.09.025. Epub 2010 Nov 5.
9
Regulation of excitability in tonic firing substantia gelatinosa neurons of the spinal cord by small-conductance Ca(2+)-activated K(+) channels.小电导钙激活钾通道对脊髓胶状质紧张性放电神经元兴奋性的调节
Neuropharmacology. 2016 Jun;105:15-24. doi: 10.1016/j.neuropharm.2016.01.001. Epub 2016 Jan 8.
引用本文的文献
1
Roles of lncLingo2 and its derived miR-876-5p in the acquisition of opioid reinforcement.lncLingo2 及其衍生的 miR-876-5p 在阿片类药物强化获得中的作用。
Addict Biol. 2024 Feb;29(2):e13375. doi: 10.1111/adb.13375.
2
SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.SK2 通道调节神经元兴奋性、突触传递和大脑节律活动在健康和疾病中的作用。
Biochim Biophys Acta Mol Cell Res. 2020 Dec;1867(12):118834. doi: 10.1016/j.bbamcr.2020.118834. Epub 2020 Aug 27.
3
Age-dependent neuroprotective effect of an SK3 channel agonist on excitotoxity to dopaminergic neurons in organotypic culture.年龄依赖性 SK3 通道激动剂对器官型培养多巴胺能神经元兴奋性毒性的神经保护作用。
PLoS One. 2020 Jul 23;15(7):e0223633. doi: 10.1371/journal.pone.0223633. eCollection 2020.
4
Genome-wide epigenetic analyses in Japanese immigrant plantation workers with Parkinson's disease and exposure to organochlorines reveal possible involvement of glial genes and pathways involved in neurotoxicity.全基因组表观遗传学分析表明，接触有机氯农药的日本移民种植园工人患帕金森病，可能涉及神经毒性的胶质基因和途径。
BMC Neurosci. 2020 Jul 10;21(1):31. doi: 10.1186/s12868-020-00582-4.
5
Primary fibroblasts from CSPα mutation carriers recapitulate hallmarks of the adult onset neuronal ceroid lipofuscinosis.CSPα 突变携带者的原代成纤维细胞再现成人发病神经元蜡样脂褐质沉积症的特征。
Sci Rep. 2017 Jul 24;7(1):6332. doi: 10.1038/s41598-017-06710-1.
6
Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.蜂毒可缓解帕金森病大鼠模型的运动功能障碍并调节通过基底神经节的皮质信息传递。
PLoS One. 2015 Nov 16;10(11):e0142838. doi: 10.1371/journal.pone.0142838. eCollection 2015.
7
Firing pattern modulation through SK channel current increase underlies neuronal survival in an organotypic slice model of Parkinson's disease.通过增加 SK 通道电流来调节放电模式是帕金森病器官切片模型中神经元存活的基础。
Mol Neurobiol. 2015 Feb;51(1):424-36. doi: 10.1007/s12035-014-8728-3. Epub 2014 May 20.
8
Subcellular expression and neuroprotective effects of SK channels in human dopaminergic neurons.人多巴胺能神经元中 SK 通道的亚细胞表达和神经保护作用。
Cell Death Dis. 2014 Jan 16;5(1):e999. doi: 10.1038/cddis.2013.530.
9
The therapeutic potential of small-conductance KCa2 channels in neurodegenerative and psychiatric diseases.小电导钙激活钾通道在神经退行性和精神疾病中的治疗潜力。
Expert Opin Ther Targets. 2013 Oct;17(10):1203-20. doi: 10.1517/14728222.2013.823161. Epub 2013 Jul 25.
10
Protective Roles for Potassium SK/K(Ca)2 Channels in Microglia and Neurons.钾 SK/Ca2 通道在小胶质细胞和神经元中的保护作用。
Front Pharmacol. 2012 Nov 26;3:196. doi: 10.3389/fphar.2012.00196. eCollection 2012.
本文引用的文献
1
Proteomics in human Parkinson's disease research.人类帕金森病研究中的蛋白质组学。
J Proteomics. 2009 Nov 2;73(1):10-29. doi: 10.1016/j.jprot.2009.07.007. Epub 2009 Jul 24.
2
Comparison of gene expression profile in embryonic mesencephalon and neuronal primary cultures.胚胎中脑与神经元原代培养物中基因表达谱的比较。
PLoS One. 2009;4(3):e4977. doi: 10.1371/journal.pone.0004977. Epub 2009 Mar 23.
3
K(+)-channel openers suppress epileptiform activities induced by 4-aminopyridine in cultured rat hippocampal neurons.钾离子通道开放剂可抑制4-氨基吡啶在培养的大鼠海马神经元中诱导产生的癫痫样活动。
J Pharmacol Sci. 2008 Dec;108(4):517-28. doi: 10.1254/jphs.08214fp. Epub 2008 Dec 11.
4
Modulation of SK channel trafficking by beta adrenoceptors enhances excitatory synaptic transmission and plasticity in the amygdala.β肾上腺素能受体对SK通道转运的调节增强了杏仁核中的兴奋性突触传递和可塑性。
J Neurosci. 2008 Oct 22;28(43):10803-13. doi: 10.1523/JNEUROSCI.1796-08.2008.
5
TNF-alpha-mediates neuroprotection against glutamate-induced excitotoxicity via NF-kappaB-dependent up-regulation of K2.2 channels.肿瘤坏死因子-α通过核因子-κB依赖的K2.2通道上调介导对谷氨酸诱导的兴奋性毒性的神经保护作用。
J Neurochem. 2008 Nov;107(4):1158-67. doi: 10.1111/j.1471-4159.2008.05701.x. Epub 2008 Sep 24.
6
Control of K(Ca) channels by calcium nano/microdomains.钙纳米/微区对钾钙通道的调控
Neuron. 2008 Sep 25;59(6):873-81. doi: 10.1016/j.neuron.2008.09.001.
7
The subthalamic nucleus. Part I: development, cytology, topography and connections.底丘脑核。第一部分：发育、细胞学、局部解剖学及连接。
Adv Anat Embryol Cell Biol. 2008;198:1-113, vii.
8
SK channel function regulates the dopamine phenotype of neurons in the substantia nigra pars compacta.小电导钙激活钾通道（SK通道）功能调节黑质致密部神经元的多巴胺表型。
Exp Neurol. 2008 Oct;213(2):419-30. doi: 10.1016/j.expneurol.2008.07.005. Epub 2008 Jul 15.
9
Protection against Parkinson's disease progression: clinical experience.预防帕金森病进展：临床经验
Neurotherapeutics. 2008 Apr;5(2):210-25. doi: 10.1016/j.nurt.2008.01.007.
10
CRF facilitates calcium release from intracellular stores in midbrain dopamine neurons.慢性肾功能衰竭促进中脑多巴胺能神经元细胞内钙库释放钙。
Neuron. 2008 Feb 28;57(4):559-70. doi: 10.1016/j.neuron.2007.12.029.
Zotero 插件