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| 1 | 抑郁症相关离子通道研究进展显示文摘抑郁症是以情绪、认知、神经内分泌和躯体功能障碍为特征的中枢系统神经疾病,是最常见的精神疾病之一。目前,抗抑郁药的治疗机制主要是以增加脑内5-羟色胺、去甲肾上腺素和多巴胺等单胺递质的浓度为主,但抑郁症仍没有得到充分的治疗。本文以离子通道为切入点,对目前研究较多的与抑郁症相关的电压门控性离子通道(如钠离子、钾离子和钙离子等)和配体门控性离子通道(如谷氨酸受体、γ-氨基丁酸受体和5-羟色胺受体等)分别予以综述,以期为抗抑郁新药的开发提供新思路。 | 吴梦瑶 赵洪庆 王宇红 | 2018 | 中国临床药理学与治疗学2018，23，8： | 4 |
| 2 | Ghrelin Reduces A-Type Potassium Currents in Dopaminergic Nigral Neurons via the PLC/PKCδPathway显示文摘Dear Editor,Ghrelin,an endogenous ligand of growth hormone secretagogue receptor 1a(GHS-R1a),is a 28-amino-acid peptide that regulates growth hormone secretion,metabolism,food intake,mood,cognition,memory,and neuroprotection[1-3]. | Bao Xue Chen Li Xiaoli Chang Hong Jiang Limin Shi Junxia Xie | 2020 | Neuroscience Bulletin2020，36，8： | 3 |
| 3 | Purinergic Receptors in Basal Ganglia Diseases:Shared Molecular Mechanisms between Huntington’s and Parkinson’s Disease显示文摘Huntington’s(HD)and Parkinson’s diseases(PD)are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms,respectively.We review here the participation of purinergic receptors through intracellular Ca^2+signaling in these neurodegenerative diseases.The adenosine A2A receptor stimulates striatopallidal GABAergic neurons,resulting in inhibitory actions on GABAergic neurons of the globus pallidus.A2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition,and A2A receptor activation results in motor inhibition.Furthermore,the A2A receptor physically and functionally interacts with glutamate receptors,mainly with the mGlu5 receptor subtype.This interaction facilitates glutamate release,resulting in NMDA glutamate receptor activation and an increase of Ca2+influx.P2X7 receptor activation also promotes glutamate release and neuronal damage.Thus,modulation of purinergic receptor activity,such as A2A and P2X7 receptors,and subsequent aberrant Ca^2+signaling,might present interesting therapeutic potential for HD and PD. | Talita Glaser Roberta Andrejew Agatha Oliveira-Giacomelli Deidiane Elisa Ribeiro Lucas Bonfim Marques Qing Ye Wen-Jing Ren Alexey Semyanov Peter Illes Yong Tang Henning Ulrich | 2020 | Neuroscience Bulletin2020，36，11： | 3 |
| 4 | 4-AP对MPTP诱导PD模型小鼠运动行为影响显示文摘目的探讨A型钾通道抑制剂4-氨基吡啶(4-AP)对l-甲基4苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠运动行为的影响。方法 8周龄雄性C57BL/6小鼠30只,随机分为对照组、MPTP组以及4-AP+MPTP组,每组10只。采用连续5d腹腔注射MPTP(30mg·kg-1·d-1)的方法制备PD小鼠模型。4-AP+MPTP组在每天注射MPTP前30min腹腔注射4-AP(1mg·kg-1·d-1),对照组以等量生理盐水代替MPTP和4-AP。连续5d注射后进行爬杆实验检测。结果 MPTP组小鼠爬杆实验的转头时间和爬杆时间明显长于对照组,而4-AP+MPTP组小鼠转头时间和爬杆时间较MPTP组明显缩短,差异均有显著意义(F=32.26、25.53,P<0.01)。结论 4-AP可使MPTP诱导的PD模型小鼠运动协调能力有所改善。 | 贾璐 石丽敏 谢俊霞 | 2019 | 青岛大学学报(医学版)2019，55，1： | 2 |
| 5 | Dopamine D2 Receptor-Mediated Modulation of Rat Retinal Ganglion Cell Excitability显示文摘Ganglion cells(RGCs) are the sole output neurons of the retinal circuity. Here, we investigated whether and how dopamine D2 receptors modulate the excitability of dissociated rat RGCs. Application of the selective D2 receptor agonist quinpirole inhibited outward K^+ currents, which were mainly mediated by glybenclamide-and 4-aminopyridine-sensitive channels, but not the tetraethylammonium-sensitive channel. In addition,quinpirole selectively enhanced Nav1.6 voltage-gated Na^+ currents. The intracellular c AMP/protein kinase A,Ca^2+/calmodulin-dependent protein kinase Ⅱ, and mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathways were responsible for the effects of quinpirole on K^+ and Na^+ currents, while phospholipase C/protein kinase C signaling was not involved. Under current-clamp conditions, the number of action potentials evoked by positive current injection was increased by quinpirole. Our results suggest that D2 receptor activation increases RGC excitability by suppressing outward K+currents and enhancing Nav1.6 currents, which may affect retinal visual information processing. | Ning Yin Yu-Long Yang Shuo Cheng Hong-Ning Wang Xin Hu Yanying Miao Fang Li Zhongfeng Wang | 2020 | Neuroscience Bulletin2020，36，3： | 2 |
| 6 | 离子通道在周围神经再生中的作用显示文摘离子通道是生物膜上一类结构和功能多样的蛋白质微孔道,广泛分布于神经系统,主要调节神经元膜电位的产生与兴奋性的传导。周围神经损伤后,初级感觉神经元上离子通道各亚型电流以及基因表达发生了较大改变。这种改变在神经病理性疼痛领域已有较多研究,但有关其在周围神经再生中的作用研究较少。由于调控离子通道生物学功能以及基因表达水平有助于周围神经损伤后的轴突生长和髓鞘再形成,故未来离子通道有望成为促进周围神经再生的新靶点。 | 崔永晨 张俊峰 | 2020 | 医学综述2020，26，22： | 1 |
| 7 | 4-氨基吡啶对MPP+诱导帕金森病细胞具有神经保护作用显示文摘目的探究4-氨基吡啶(4-aminopyridine,4-AP)对1-甲基-4-苯基吡啶离子(1-methyl-4-phenylpyridinium,MPP+)诱导的帕金森病细胞模型是否存在保护作用。方法利用不同浓度的MPP+孵育SH-SY5Y细胞,探究不同浓度MPP+对细胞活性的影响。单独利用4-AP孵育细胞,探究4-AP是否影响细胞活性。利用4-AP预处理SH-SY5Y细胞系24h后,随后选取合适浓度的MPP+孵育细胞24h,CCK8测定细胞活性并进行统计学分析。结果随着MPP+药物浓度的升高,SH-SY5Y细胞活性下降。不同浓度的4-AP单独孵育SH-SY5Y细胞系对细胞活性不产生影响。不同浓度的4-AP预处理细胞24h后,加入1mol/L的MPP+孵育24h,当4-AP浓度在0.3~10mol/L时SH-SY5Y细胞的活性增加,在1mol/L时细胞活性增加最佳,为正常细胞的66%。结论一定浓度范围内的4-AP可减少MPP+对SH-SY5Y细胞的毒性作用,具有神经保护作用。 | 马媛媛 周畅 陈枫蕾 容琼文 | 2023 | 中国现代医生2023，61，1： | 1 |
| 8 | A型钾通道在正常大鼠小脑皮层中的表达显示文摘目的探讨5种A型钾通道亚型Kv4.1、Kv4.2、Kv4.3、Kv3.4和Kv1.4在正常大鼠小脑皮层中的表达。方法采用免疫荧光染色技术和实时荧光定量聚合酶链反应(qRT-PCR)检测健康成年雄性SD大鼠小脑皮层的A型钾通道亚型的分布。结果采用qRT-PCR技术在6只大鼠小脑皮层均检测到了Kv4.1、Kv4.2、Kv4.3、Kv3.4和Kv1.4mRNA表达,其中,Kv4.3mRNA表达丰度最高,其次是Kv4.2和Kv3.4,且Kv4.3、Kv4.2和Kv3.4mRNA表达丰度明显高于Kv1.4和Kv4.1mRNA;免疫荧光染色实验表明,Kv3.4、Kv4.2和Kv4.3蛋白分布于不同的小脑皮层细胞群,Kv3.4表达在小脑普肯野氏细胞,在颗粒细胞未见Kv3.4阳性产物;Kv4.2表达在小脑颗粒细胞,在普肯野氏细胞未见Kv4.2阳性产物;而Kv4.3在小脑普肯野氏细胞和颗粒细胞均有表达。结论正常大鼠小脑皮层中存在A型钾通道表达,其主要亚型为Kv3.4、Kv4.2和Kv4.3,且不同亚型在小脑皮层不同神经细胞群上分布不同。 | 王斯颖 余鑫钰 杨培培 刘茂雪 胡红利 唐新 邓杰文 黄成 张洁 林友胜 | 2020 | 成都医学院学报2020，15，1： | 0 |
| 9 | 士的宁对Kv4.3钾通道的影响显示文摘目的 探究士的宁对Kv4.3钾通道的影响。方法 于2019年6—10月在大连理工大学以HEK293T细胞为载体,瞬时转染Kv4.3钾通道,形成Kv4.3-HEK293T细胞,一共选取24个Kv4.3-HEK293T细胞,采用全细胞膜片钳技术,加药前记录的数据为对照组,1μmol/L士的宁处理后的数据为观察组,研究士的宁对Kv4.3电流和动力学参数的影响。结果 与对照组相比,1μmol/L士的宁能抑制Kv4.3电流;1μmol/L士的宁能使半数激活电压由(15.41±2.87)mV降到(-2.10±2.08)mV,差异有统计学意义(t=12.101,P<0.001);1μmol/L士的宁能使半数失活电压降低,但差异无统计学意义(P>0.05);1μmol/L士的宁能使失活后恢复时间τ由(38.64±2.10)ms增加到(48.52±2.79)ms,差异有统计学意义(t=6.930,P<0.001)。结论 士的宁作为中枢兴奋药,其作用机制是可以通过影响Kv4.3钾通道的激活和失活后恢复过程来抑制Kv4.3钾电流。 | 赵晓燕 张勇刚 高瑞娜 赵一彧 | 2023 | 系统医学2023，8，9： | 0 |
| 10 | A53T转基因小鼠黑质Kv4.3 A型钾通道的表达改变显示文摘目的探讨不同月龄α-突触核蛋白A53T转基因小鼠黑质区Kv4.3 A型钾通道的表达变化。方法选取不同月龄A53T转基因小鼠和同窝野生型(WT)对照小鼠,采用蛋白免疫印迹(Western blot)方法检测小鼠黑质区Kv4.3以及酪氨酸羟化酶(TH)蛋白的表达。结果3月龄的A53T转基因小鼠Kv4.3及TH蛋白的表达与WT小鼠比较差异无显著性(P>0.05),15月龄的A53T转基因小鼠Kv4.3蛋白表达较WT小鼠升高(t=3.202,P<0.01),TH蛋白表达较WT小鼠降低(t=2.475,P<0.05)。结论黑质区Kv4.3 A型钾通道随着帕金森病(PD)病情的进展发生改变,可能参与了PD的发病过程。 | 王怡云 石丽敏 谢俊霞 | 2021 | 青岛大学学报(医学版)2021，57，2： | 0 |
| 11 | 内源性大麻素2-AG对海人藻酸诱导损伤的大鼠尾状核神经元A型钾通道电流的调制作用显示文摘目的:研究内源性大麻素2-花生四烯酰甘油(2-AG)对海人藻酸(KA)损伤的A型钾通道的调制作用及其分子机制。方法:用KA处理原代培养的大鼠尾状核(CN)神经元,建立神经兴奋性毒性细胞模型;通过全细胞膜片钳记录,观察KA介导的兴奋性毒性及2-AG的神经保护作用过程中CN神经元上A型钾通道电学功能的改变。结果:在培养的大鼠尾状核神经元上,膜片钳实验显示KA明显降低CN神经元A型钾通道电流(I_(A))密度并改变通道电学功能:失活曲线斜率(k)和失活后恢复时间常数(τ)均显著增大。细胞孵育液中直接加入内源性大麻素2-AG或单酰甘油脂肪酶抑制剂URB602使2-AG水解减少而间接升高细胞内2-AG水平,均可通过大麻素受体1(CB1R)抑制KA诱导的I_(A)密度降低,有效拮抗KA所致A型钾通道τ值和k值的增大,加快A型钾通道失活后恢复过程。结论:A型钾通道电学特性的改变可能是KA造成CN神经元兴奋性毒性损伤的机制之一。2-AG可通过CB1R途径调节A型钾通道功能,从而起到神经保护作用。 | 朱时钰 陆永利 李自成 杨红卫 | 2023 | 中国病理生理杂志2023，39，12： | 0 |
| 12 | A Novel Potassium Nanosensor Powers up the Detection of Extracellular K+ Dynamics in Neuroscience显示文摘Potassium ions(K+),the pivotal cations for membrane potential,are particularly important for maintaining the physiological function of neurons[1].When the concentration of extracellular K+([K+]o)is pathologically changed,the intrinsic neuronal excitability and synaptic transmission are also altered,which have profound implications for many neurological disorders such as epilepsy,Parkinson's disease,and emotional disorders[2-4]. | Ying Wang Qingyu Wang Xia Zhang | 2020 | Neuroscience Bulletin2020，36，12： | 0 |
| 13 | Joint Multi-modal Parcellation of the Human Striatum:Functions and Clinical Relevance显示文摘The human striatum is essential for both lowand high-level functions and has been implicated in the pathophysiology of various prevalent disorders,including Parkinson's disease(PD)and schizophrenia(SCZ).It is known to consist of structurally and functionally divergent subdivisions.However,previous parcellations are based on a single neuroimaging modality,leaving the extent of the multi-modal organization of the striatum unknown.Here,we investigated the organization of the striatum across three modalities—resting-state functional connectivity,probabilistic diffusion tractography,and structural covariance—to provide a holistic convergent view of its structure and function.We found convergent clusters in the dorsal,dorsolateral,rostral,ventral,and caudal striatum.Functional characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions,while the caudal striatum was related to action execution.Interestingly,significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ,but atrophy in the dorsolateral striatum was specifically attributable to PD.Our study revealed a cross-modal convergent organization of the striatum,representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions. | Xiaojin Liu Simon B.Eickhoff Felix Hoffstaedter Sarah Genon Svenja Caspers Kathrin Reetz Imis Dogan Claudia R.Eickhoff Ji Chen Julian Caspers Niels Reuter Christian Mathys Andre Aleman Renaud Jardri Valentin Riedl Iris E.Sommer Kaustubh R.Patil | 2020 | Neuroscience Bulletin2020，36，10： | 0 |
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