易鸣，中国科学院武汉物理与数学研究所副研究员。 http://www.researcherid.com/rid/B-5383-2011 统计物理专业出生，自2001年起一直从事生物系统随机动力学的研究，在基因调控网络以及神经网络的随机理论和应用上积累了一定的基础，主要包括：研究了随机噪声对于果蝇的单细胞昼夜生理节律振子的影响。当节律振子只被外部光噪声驱动时，发现外噪声可以诱导相干共振现象（Phys. Rev. E 72，012902 (2005)）；当内噪声和外噪声同时驱动系统时，我们发现外噪声在一定的噪声强度范围能够促进“内噪声相干共振”，这是随机噪声起积极作用的一个典型例子（Phys. Rev. E 73，041923 (2006)）；依据一个大肠杆菌质粒体的拷贝数控制模型，理论研究发现：在一定的参数范围内，增加信号分子的噪声强度会减少质粒体分子的噪声强度，推导得到了这种噪声降低效应发生的临界条件（Phys. Rev. E 77，022902 (2008)）；研究了单个双稳的神经元在加性以及乘性噪声作用下分别诱导相干共振过程中的不同动力学机制（Phys. Rev. E 77, 061905 (2008)）；探讨了一个多层前馈型神经元网络模型，通过数值模拟发现，高斯白噪声在第一层激发产生不规则的神经触发行为，经过该多层神经元网络后，神经元的电兴奋会慢慢变得同步，进一步分析了网络连接结构对于同步触发的影响（Phys. Rev. E 81，061924 (2010)）；研究了小世界神经网络中神经元的同步动力学，发现时间延迟以及神经差异性能够诱导网络同步性质发生丰富的转变，通过时空斑图以及同步指标定性以及定量的阐述了同步转变的机制（Phys. Rev. E 83, 046207 (2011) ）。 近四年来，重点研究信号转导网络的数学建模和动力学分析，在研究酶的反应扩散体系方面取得了如下工作：基于离散的固定步长随机行走蒙特卡洛数值模拟研究了微观条件下的米氏动力学，得到了单酶条件下的酶催化速率，并探讨了扩散速率的变化对于米氏曲线的影响（Physica A 389,3791 (2010)），同时研究了多酶的MAPK级联模块中支架蛋白对于信号放大的影响，发现慢的去磷酸化情形下，支架蛋白的结合有利于信号放大，而支架蛋白的数目则抑制了信号放大；快的去磷酸化情形下，支架蛋白的结合削弱了信号放大。这些定性的结论都在真实的生物体系中被观察到（Biophys. Chem. 147, 130 (2010)）；基于常规的整数阶“反应扩散方程”，建立了MAPK信号级联从细胞膜到细胞质空间的反应扩散模型，研究发现MAPK级联处于超灵敏、磷酸化环局部双稳、级联全局双稳以及振荡等四种不同的操作模式下时，活性激酶的空间分布以及药剂依赖关系具有非常不同的响应特点（Phys. Biol. (2011)接收待发表），其次，我们提出了一个整合的生物网络模型，将钙离子振荡模块、GTPase环模块以及MAPK级联模块依次结合起来,研究了振荡的钙信号对于MAPK活性的影响，动力学分析表明：MAPK模块合适的操作模式以及GTPase环模块合理的参数取值对于重现实验现象是十分关键的（Biophys. Chem. 157 (2011) 33）。 文章列表 1. Delay and diversity-induced synchronization transitions in a small-world neuronal network， Jun Tang, Jun Ma, Ming Yi , Hui Xia, and Xianqing Yang, Physical Review E. 83, (2011) 046207 2. Spatial distribution and dose response for different operation modes in a reaction-diffusion model of MAPK cascade, Qi Zhao, Ming Yi*, Yan Liu, Physical Biology. (2011) accepted for publication. 3. A theoretical modeling for frequency modulations of Ca2+ signal on activation of MAPK cascade, Ming Yi* and Qi Zhao, Biophysical Chemistry. 157 (2011) 33 4. Michaelis-Menten mechanism for single-enzyme and multi-enzyme system under stochastic noise and spatial diffusion Author(s): Yi, M; Liu, QA Source: Physica a-Statistical Mechanics and Its Applications Volume: 389 Issue: 18 Pages: 3791-3803 Published: 2010 5. Propagation of firing rate by synchronization and coherence of firing pattern in a feed-forward multilayer neural network Author(s): Yi, M; Yang, LJ Source: Physical Review E Volume: 81 Issue: 6 Published: 2010 6. Theoretical study for regulatory property of scaffold protein on MAPK cascade: A qualitative modeling Author(s): Yi, M ; Xia, KL; Zhan, M Source: Biophysical Chemistry Volume: 147 Issue: 3 Pages: 130-139 Published: 2010 7. A constructive role of internal noise on coherence resonance induced by external noise in a calcium oscillation system Author(s): Yu, G; Yi, M; Jia, Y; et al. Source: Chaos Solitons Fractals Volume: 41 Issue: 1 Pages: 273-283 Published: 2009 8. Cooperative effects of noise and coupling on stochastic dynamics of a membrane-bulk coupling model Author(s): Tang, J; Jia, Y; Yi, M Source: Communications in Theoretical Physics Volume: 51 Issue: 3 Pages: 455-459 Published: 2009 9. Information propagation from IP3 to target protein: A combined model for encoding and decoding of Ca2+ signal Author(s): Zhao, Q; Yi, M; Xia, KL; et al. Source: Physica a-Statistical Mechanics and Its Applications Volume: 388 Issue: 19 Pages: 4105-4114 Published: 2009 10. Suppression of spiral wave and turbulence by using amplitude restriction of variable in a local square area Author(s): Ma, J; Jia, Y; Yi, M; et al. Source: Chaos Solitons Fractals Volume: 41 Issue: 3 Pages: 1331-1339 Published: 2009 11. Theoretical Study on Drift of Ca2+ Spiral Waves Controlled by Electric Field Author(s): Tang, J; Jia, Y; Ma, J; et al. Source: Communications in Theoretical Physics Volume: 51 Issue: 5 Pages: 941-946 Published: 2009 12. Control of spiral wave and turbulence in the time-varied reaction-diffusion system Author(s): Ma, J; Jin, WY; Yi, M; et al. Source: Acta Physica Sinica Volume: 57 Issue: 5 Pages: 2832-2841 Published: 2008 13. Coupling effect of ion channel clusters on calcium signalling Author(s): Tang, J; Jia, Y; Yi, M; et al. Source: Chinese Physics Letters Volume: 25 Issue: 3 Pages: 1149-1152 Published: 2008 14. Critical condition for the occurrence of a noise-reduction effect Author(s): Yi, M; Jia, Y; Ma, J; et al. Source: Physical Review E Volume: 77 Issue: 2 Published: 2008 15. Evolution of spiral wave and pattern formation in a vortical polarized electric field Author(s): Ma, J; Yi, M; Li, BW; et al. Source: Chinese Physics B Volume: 17 Issue: 7 Pages: 2438-2445 Published: 2008 16. Multiplicative-noise-induced coherence resonance via two different mechanisms in bistable neural models Author(s): Tang, J; Jia, Y; Yi, M; et al. Source: Physical Review E Volume: 77 Issue: 6 Published: 2008 17. Numerical study of IP3-dependent Ca2+ spiral waves in Xenopus oocytes Author(s): Tang, J; Jia, Y; Ma, J; et al. Source: Epl Volume: 83 Issue: 6 Published: 2008 18. RyR channels and glucose-regulated pancreatic beta-cells Author(s): Zhan, X; Yang, L; Yi, M; et al. Source: European Biophysics Journal With Biophysics Letters Volume: 37 Issue: 6 Pages: 773-782 Published: 2008 19. Stabilization of pattern in complex Ginzburg-Landau equation with spatial perturbation scheme Author(s): Ma, J; Yi, M; Zhang, LP; et al. Source: Communications in Theoretical Physics Volume: 49 Issue: 6 Pages: 1541-1546 Published: 2008 20. Title: Suppression of spiral wave in modified Orengonator model Author(s): Ma, J; Jin, WY; Yi, M ; et al. Source: Communications in Theoretical Physics Volume: 50 Issue: 2 Pages: 403-410 Published: 2008 21. Title: Theoretical study of mesoscopic stochastic mechanism and effects of finite size on cell cycle of fission yeast Author(s): Yi, M; Jia, Y; Tang, J; et al. Source: Physica a-Statistical Mechanics and Its Applications Volume: 387 Issue: 1 Pages: 323-334 Published: 2008 22. Title: A coarse estimation of cell size region from a mesoscopic stochastic cell cycle model Author(s): Yi, M ; Jia, Y; Liu, Q; et al. Source: Chinese Physics Letters Volume: 24 Issue: 7 Pages: 1829-1832 Published: JUL 2007 23. Title: Enhancement of internal-noise coherence resonance by modulation of external noise in a circadian oscillator Author(s): Yi, M ; Jia, Y; Liu, Q; et al. Source: Physical Review E Volume: 73 Issue: 4 Published: APR 2006 24. Title: Light-noise-induced suprathreshold circadian oscillations and coherent resonance in Drosophila Author(s): Yi, M ; Jia, Y Source: Physical Review E Volume: 72 Issue: 1 Published: JUL 2005 ========================================================================== 25. Lijian Yang, Ya Jia, Ming Yi ,The effects of electrical coupling on the temporal coding of neural signal in noisy Hodgkin-Huxley neuron ensemble International Conference on Natural Computation.10, 819（2010）(EI). 26. Ming Yi, Guang Yu, Jun Tang, Jun Ma, Ya Jia, Effects of structural diversity and fluctuations on synchronization of coupled circadian oscillators, International Journal of Biomedical Soft Computing and Human Sciences. 14, (2009) 67. 27. Spatiotemporal stochastic resonance in a bistable FitzHugh-Nagumo ring with phase-repulsive coupling Qi Zhao Ming Yi* Chenggui Yao EPJB 2011 in revise
今天无聊看了些咨询，不过倒是读了一个挺有意思的文章，是 Nature Feb 10 Title：Functional identification of an aggression locus in the mouse hypothalamus。 大意说的是小鼠负责攻击性和交配的神经元可能是部分重叠，但又有distinct subpopulation。“Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviors.” 引申一下就是说对小鼠来说性可能会化解暴力，这在人类身上也可能适用。 当时大学不知道是上什么课的时候听到了美国的这么一句话- Make love not war .说的是美国60年代反文化运动的时候，年轻人对老美针对越战提出的看法。现在看看，真是简洁，给力，生动，具体。想想现在埃及的局势，虽然还没有说到战争的地步，不过也是乱的一团糟，不知道穆巴拉克如果看到nature这篇文章，想到Make love not war，我觉得如果他以这个作为宣传口号的话，有可能还会对局势有一些缓解（如果真是这样那一切就简单了）。 说到埃及，早上看同学分享的奥巴马关于埃及的演讲，他用的是“The spirit of peaceful protest and the perseverance that the Egypt people have shown can serve as a powful wind at the back of this change. The united state will continue to be a friend and a partner to Egypt. We stand ready for whatever assistance necessary. And ask for to pursue a credible transition to democracy.”（不一定听得全对）也就是和平过渡，但每天CNN上面报到的死亡人数，似乎告诉我情况并不太平。 政治太复杂，这个是我和我们楼里一个老美（真挺老的）聊天的时候最后达成的共识。 首先各种因素牵涉其中，局外人很难分清什么才是真正的动机，甚至局内人可能也会因为事件的复杂以及各种机遇的出现而变更最初的想法，并且最终获利。 其次作为大众，获得信息的渠道是在是太有限了，CNN已经是投机倒把，BBC还算是在追求unbias的媒体，twitter虽然真实但是太零散，很容易让一个疯狂转载了1万次的状态放大了真实的情况。 还有，现在信息量太大，各个媒体为了追求自身利益而采取“修辞手段”，“独特视角”来诠释同一个问题，很容易让人产生迷惑，到底事情的真相是什么呢？很难知道。Wikileaks就是一个典型。 所以有的时候觉得搞科研还是挺幸福的。同样是对问题的好奇，政治你需要太多的人脉，资金，精力才可以介入，而科学主要需有一个好的实验室，和一个爱思考的大脑，就不妨碍你的信马由缰。相比生物，限制更少的还要算是数学和计算机，只要一个PC，同时身在中国，就可以任意发挥了（羡慕你们）。可惜已经选了生物这个不归路，只能这样走下去。希望未来还能有好奇心，开心点把科研搞好。 对文章感兴趣的同学可以看： Nature doi:10.1038/nature09736 Functional identification of an aggression locus in the mouse hypothalamus Dayu Lin1, 2 Maureen P. Boyle3 Piotr Dollar4 Hyosang Lee1 E. S. Lein3 Pietro Perona4 David J. Anderson1, 2 Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.
http://www.gopubmed.org/web/gopubmed/1?WEB01kqpckyo8hmcqI1mI1I00f01000j10040001rl ((memories and hippocampus and neurogenesis) =Memory ) =Neurons 16 of 33 documents semantically analyzed Top Years Publications 2007 5 2009 3 2001 3 2006 2 2008 1 2005 1 2004 1 Top Countries Publications USA 7 France 3 Argentina 1 Italy 1 China 1 Canada 1 Germany 1 Top Cities Publications Orsay 3 Buenos Aires 1 Rome 1 Nanjing 1 Baltimore 1 Toronto 1 Freiburg 1 Princeton 1 Houston 1 Top Journals Publications Neuron 3 Nature 2 Cognition 1 Proc Natl Acad Sci U S A 1 Plos Biol 1 Neuroscientist 1 Rev Neurosci 1 J Neurosci Res 1 Hippocampus 1 Neurosurg Clin N Am 1 J Neurosci 1 Nat Neurosci 1 Neuroscience 1 1 2 3 ... 9 Top Terms Publications Neurons 16 Adult 16 Memory 16 Hippocampus 15 neurogenesis 15 Animals 14 hippocampus development 11 learning 10 Dentate Gyrus 10 Neuronal Plasticity 10 learning or memory 8 Humans 8 dentate gyrus development 8 Stem Cells 7 Cell Differentiation 7 Cell Proliferation 6 Plastics 6 Rats 5 homeostasis of number of cells 4 Learning 4 1 2 3 ... 9 1 2 3 4 Top Authors Publications Laroche S 3 Bruel-Jungerman E 3 Shors T 2 Gage F 2 Davis S 2 Rampon C 2 Dalla C 1 Papachristos E 1 Whetstone A 1 Aimone J 1 Wiles J 1 Tirone F 1 Farioli-Vecchioli S 1 Saraulli D 1 Costanzi M 1 Pacioni S 1 Cin I 1 Aceti M 1 Micheli L 1 Bacci A 1 1 2 3 4 http://www.sciencenet.cn/htmlnews/2009/11/225173.shtm 《细胞》：科学家首次证明神经元的形成能清除旧有记忆 海马神经元 据国外媒体报道，日本科学家11月13日在《细胞》（ cell ）杂志上发表研究文章称，新生脑细胞能破坏大脑海马区的脑细胞之间的联系。海马区是脑部和学习及记忆有关的区域。科学家表示，清除大脑旧有记忆能够为学习新知识提供空间。 加拿大多伦多病患儿童医院神经科学家保罗-弗兰科兰表示，此前已经有科研人员提出神经元的形成能够清除旧有记忆的观点，但是日本科学家在《细胞》杂志发表的文章是首个找到证据证明这一观点的研究。上个世纪50年代，科学家发现大脑中的海马区在存储信息的过程中扮演着至关重要的角色，如果切除掉海马区，那么以前的记忆就会一同消失。科学家已经知道记忆最初在大脑海马区形成，而后转移到大脑其他区域长期保存。海马体主要负责学习和记忆，日常生活中的短期记忆都储存在海马体中，如果一个记忆片段，比如一个电话号码或者一个人在短时间内被重复提及的话海马体就会将其转存入大脑皮层，成为永久记忆。在一段时间内，记忆在海马区和脑部其他区域共存。不过科学家仍未了解的是，经过数月或数年后记忆是如何被从海马区清除的？海马区的神经细胞如何把信息固定下来？ 日本富山大学神经学家井口薰和他的同事利用辐射和其他基因方法，阻止老鼠脑部神经元形成。这些老鼠被置于特别的笼子内，科学家训练它们对轻微的电击感到恐惧。科学家发现，这些老鼠只能依赖海马区唤回恐惧记忆。而对比组老鼠，大脑神经元的形成并未受到阻滞，它们能够跳过海马区从脑部长期储存中找回恐惧记忆。科研人员还发现，通过一些有助于神经元形成的运动，老鼠的旧有记忆从海马区被清除的速度加快。不过井口薰表示，研究结果并不意味着新生神经元在大脑形成新记忆方面不必要。 科研人员还探讨了神经元形成在学习和记忆中的作用。海马区是成年人大脑中形成新神经元的两个区域之一。此前的研究认为，新生神经元能够加固记忆电路。但是日本科学家的最新研究却推翻了这一观点，新神经元削弱甚至破坏海马区为旧有记忆编码的脑细胞之间的联系。 井口薰说：我们的发现并没有否认神经元形成在获得记忆方面的重要作用。海马区神经元形成不但能清除旧记忆，还能获得新记忆。从本质上讲，新神经元通过防止海马区被大量旧记忆塞满而形成新记忆。 更多阅读 《连线》相关报道（英文） 《细胞》发表论文摘要（英文） http://www.wired.com/wiredscience/2009/11/new-brain-cells-may-knock-out-old-memories/?utm_source=feedburnerutm_medium=feedutm_campaign=Feed%3A+wired%2Fscience+(Wired%3A+Science ) New Brain Cells May Knock Out Old Memories By Tina Hesman Saey, Science News November 12, 2009 | 5:44 pm | Categories: Brains and Behavior Old memories may get the boot from new brain cells. A new rodent study shows that newborn neurons destabilize established connections among existing brain cells in the hippocampus, a part of the brain involved in learning and memory. Clearing old memories from the hippocampus makes way for new learning, researchers from Japan suggest in the November 13 Cell . Other researchers had proposed the idea that neurogenesis, the birth of new neurons, could disrupt existing memories, but the Cell paper is the first to show evidence supporting the idea, says Paul Frankland, a neuroscientist at the Hospital for Sick Children in Toronto. Scientists have known that memories first form in the hippocampus and are later transferred to long-term storage in other parts of the brain. For some amount of time the memory resides both in the hippocampus and elsewhere in the brain. Whats not been known is how, after a few months or years, the memory is gradually cleared from the hippocampus. Researchers have also debated the role of neurogenesis in learning and memory. The hippocampus is one of only two places in the adult brain where scientists know that new neurons form. On the basis of previous studies, many researchers think new neurons stabilize memory circuits or are somehow otherwise necessary to form new memories. The new study suggests the opposite: Newborn neurons weaken or disrupt connections that encode old memories in the hippocampus. Kaoru Inokuchi, a neuroscientist at the University of Toyama in Japan, and his colleagues used radiation and some genetic tricks to block neurogenesis in rats and mice that had been trained to fear getting a mild electric shock when placed in a particular cage. Control animals, with normal neurogenesis, eventually were able to bypass their hippocampi and retrieve the fear memory directly from long-term storage. But animals in which neurogenesis had been blocked still depended on the hippocampus to recall the fear memory, the researchers found. Running on an exercise wheel, which boosts neurogenesis, also sped the rate at which old memories were cleared from the hippocampus. But that doesnt mean new neurons arent necessary to teach old brains new tricks, says Inokuchi. Our findings do not necessarily deny the important role of neurogenesis in memory acquisition, Inokuchi says. Hippocampal neurogenesis could have both of these roles, in erasing old memories and acquiring new memories. Essentially, the new neurons may aid formation of new memories by keeping the hippocampus from filling up with old ones. Frankland adds, This is about as novel as it gets in the field of neurogenesis and memory. It pretty much represents an entirely new framework that other researchers will chip away at for years to come. Image: Hippocampal neuron/NIH See Also: Memory Switch Could Enable Brain Hacks The Messy Future of Memory-Editing Drugs Memory Disruption Could Aid Addicts Video: US Memory Champ Helps You Program Your Memory Marijuana Could Be Good for Memory But Not if You Get High http://www.cell.com/abstract/S0092-8674(09)01309-9 Adult Neurogenesis Modulates the Hippocampus-Dependent Period of Associative Fear Memory Takashi Kitamura 1 , 2 , 3 , Yoshito Saitoh 1 , 2 , 3 , Noriko Takashima 1 , 3 , Akiko Murayama 1 , 3 , Yosuke Niibori 1 , 3 , 5 , Hiroshi Ageta 1 , 6 , Mariko Sekiguchi 1 , 3 , Hiroyuki Sugiyama 4 and Kaoru Inokuchi 1 , 2 , 3 , , 1 Mitsubishi Kagaku Institute of Life Sciences, MITILS, 11 Minamiooya, Machida, Tokyo, 194-8511, Japan 2 Department of Biochemistry, Faculty of Medicine, Graduate School of Medicine Pharmaceutical Sciences, University of Toyama, 2630Sugitani, Toyama 930-0194, Japan 3 Japan Science and Technology Agency, CREST, Kawaguchi 332-0012, Japan 4 Department of Biology, Graduate School of Science, Kyushu University, Fukuoka 812-8581, Japan Corresponding author 5 Present address: Program in Neurosciences and Mental Health, Hospital for Sick Children Research Institute, Toronto, Canada M5G 1X8 6 Present address: Institute for Comprehensive Medical Science, Fujita Health University, Aichi 470-1192, Japan Summary Acquired memory initially depends on the hippocampus (HPC) for the process of cortical permanent memory formation. The mechanisms through which memory becomes progressively independent from the HPC remain unknown. In the HPC, adult neurogenesis has been described in many mammalian species, even at old ages. Using two mouse models in which hippocampal neurogenesis is physically or genetically suppressed, we show that decreased neurogenesis is accompanied by a prolonged HPC-dependent period of associative fear memory. Inversely, enhanced neurogenesis by voluntary exercise sped up the decay rate of HPC dependency of memory, without loss of memory. Consistently, decreased neurogenesis facilitated the long-lasting maintenance of rat hippocampal long-term potentiation invivo. These independent lines of evidence strongly suggest that the level of hippocampal neurogenesis play a role in determination of the HPC-dependent period of memory in adult rodents. These observations provide a framework for understanding the mechanisms of the hippocampal-cortical complementary learning systems.
http://www.sciencenet.cn/htmlnews/2009/8/222290.shtm 科学家们已经查明了小鼠体内的一组对瘙痒刺激进行反应的神经元，该组神经元会通知脑部现在是开始瘙抓的时候了。这些发现本身也挠到了神经科学一个长期的痒处：即神经系统是否对痛觉和瘙痒的感觉以同样的方式进行处置。研究人员对瘙痒是否基本上不过是疼痛的一种形式或体内是否有专门的瘙痒、疼痛及其他感觉（即所谓的标示线路假设）的神经通路进行过辩论。迄今为止，有关这一假说的证据仍然不甚一致，但由Yan-Gang Sun所做的一项新的研究应该有助于息止这一争议。研究人员过去曾经确认了一种叫做GRPR的神经元受体是感受瘙痒刺激但却不感受疼痛刺激的受体。现在，这些研究人员证明，那些脊髓中缺乏GRPR受体神经元的小鼠不会对瘙痒刺激进行挠抓反应，但它们感受疼痛的能力则与正常小鼠一样。结果，这类表达GRPR的神经元被发现与另外一组叫做SST的神经元是不同的，而这曾经是人们过去争辩的焦点。这些新的发现因而提示，表达GRPR的神经元是一个人们长期以来寻找的脊髓中的瘙痒感觉标示线路的组成成分。 信息分析平台： http://www.gopubmed.org/web/gopubmed/1?WEB01mdyex09iu5ukImI1I00c000j10040001rl 检索策略：GRPR and pruritus 分析结果： Top Years Publications 2008 1 2007 1 Top Countries Publications Canada 1 USA 1 Top Cities Publications Calgary 1 St. Louis 1 Top Journals Publications J Hepatol 1 Nature 1 Top Authors Publications Swain M 1 Chen Z 1 Sun Y 1 1 2 3 Top Terms Publications central nervous system maturation 2 central nervous system development 2 central nervous system formation 2 central nervous system morphogenesis 2 dorsal spinal cord development 2 cerebrospinal fluid secretion 2 gastrin-releasing peptide receptor binding 2 behavioral response to pain 2 spinal cord development 2 inflammatory response 2 response to pain 2 Receptors, Peptide 2 Spinal Nerve Roots 2 Spinal Cord 2 Skin Diseases 2 Liver Diseases 2 Ganglia, Spinal 2 Dermatitis, Atopic 2 Cerebrospinal Fluid 2 Gastrin-Releasing Peptide 2 1 2 3 相关文献： Gastrin-releasing peptide and pruritus : more than just scratching the surface. PMID: 18280606 Related Articles Authors: Swain, M G Journal: J Hepatol , Vol. 48 (4): 681-3 , 2008 Abstract: A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Sun YG, Chen ZF. Itching, or pruritus , is defined as an unpleasant cutaneous sensation that serves as a physiological self-protective mechanism to prevent the body from being hurt by harmful external agents. Chronic itch represents a significant clinical problem resulting from renal diseases and liver diseases, as well as several serious skin diseases such as atopic dermatitis. The identity of the itch-specific mediator in the central nervous system, however, remains elusive. Here we describe that the gastrin-releasing peptide receptor ( GRPR ) plays an important part in mediating itch sensation in the dorsal spinal cord. We found that gastrin-releasing peptide is specifically expressed in a small subset of peptidergic dorsal root ganglion neurons, whereas expression of its receptor GRPR is restricted to lamina I of the dorsal spinal cord. GRPR mutant mice showed comparable thermal, mechanical, inflammatory and neuropathic pain responses relative to wild-type mice. In contrast, induction of scratching behaviour was significantly reduced in GRPR mutant mice in response to pruritogenic stimuli, whereas normal responses were evoked by painful stimuli. Moreover, direct spinal cerebrospinal fluid injection of a GRPR antagonist significantly inhibited scratching behaviour in three independent itch models. These data demonstrate that GRPR is required for mediating the itch sensation rather than pain, at the spinal level. Our results thus indicate that GRPR may represent the first molecule that is dedicated to mediating the itch sensation in the dorsal horn of the spinal cord, and thus may provide a central therapeutic target for anti-pruritic drug development. Affiliation: Liver Unit, University of Calgary, Health Sciences Center, 3330 Hospital Drive, NW, Calgary , Alta., Canada T2N 4N1. swain@ucalgary.ca Title: A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. PMID: 17653196 Related Articles Authors: Sun, Y G , Chen, Z F Journal: Nature , Vol. 448 (7154): 700-3 , 2007 Abstract: Itching, or pruritus , is defined as an unpleasant cutaneous sensation that serves as a physiological self-protective mechanism to prevent the body from being hurt by harmful external agents. Chronic itch represents a significant clinical problem resulting from renal diseases and liver diseases, as well as several serious skin diseases such as atopic dermatitis. The identity of the itch-specific mediator in the central nervous system, however, remains elusive. Here we describe that the gastrin-releasing peptide receptor ( GRPR ) plays an important part in mediating itch sensation in the dorsal spinal cord. We found that gastrin-releasing peptide is specifically expressed in a small subset of peptidergic dorsal root ganglion neurons, whereas expression of its receptor GRPR is restricted to lamina I of the dorsal spinal cord. GRPR mutant mice showed comparable thermal, mechanical, inflammatory and neuropathic pain responses relative to wild-type mice. In contrast, induction of scratching behaviour was significantly reduced in GRPR mutant mice in response to pruritogenic stimuli, whereas normal responses were evoked by painful stimuli. Moreover, direct spinal cerebrospinal fluid injection of a GRPR antagonist significantly inhibited scratching behaviour in three independent itch models. These data demonstrate that GRPR is required for mediating the itch sensation rather than pain, at the spinal level. Our results thus indicate that GRPR may represent the first molecule that is dedicated to mediating the itch sensation in the dorsal horn of the spinal cord, and thus may provide a central therapeutic target for antipruritic drug development. Affiliation: Department of Anesthesiology, Washington University School of Medicine Pain Center, St Louis , Missouri 63110, USA .
工频电磁场对皮层神经元瞬时外向钾电流的影响 1. 引言 随着现代科技的进步和社会经济的迅猛发展，各种电子产品、电力设备被大量的应用到人们生活环境中，人为产生的电磁场已逐渐成为威胁人体以及其他生物体健康和安全的环境污染因子。电磁辐射污染，又称电磁污染，已成为继大气污染、水污染和噪声污染后的第四污染 。工频电磁场 (power frequency electromagnetic field) 是由输电线及家用电器 所产生的一种极低频电磁场 ，我国采用 50Hz 为工作频率，而西方一些国家 ( 如美国、加拿大 ) 使用 60Hz 。 人类接触这种极低频电磁场的机会远远多于其他频段的电磁场和天然磁场，有研究表明，极低频电磁场可能与肿瘤、胚胎畸形以及神经、心血管、免疫、内分泌、生殖等器官系统的病变相关 。极低频电磁场暴露能增加肿瘤(尤其是白血病、脑瘤和乳腺癌等)发生的危险度 ，在一定程度上具有促癌效应 ；细胞分子水平上的很多研究提示，环境中的极低频电磁场可能具有潜在的生物学危害 ；但是也有相当一部分研究结果对此持否定或矛盾的观点 。工频电磁场暴露可导致小鼠精子数量、活力下降，精子头部畸形率上升 ；50Hz正弦磁场暴露引起鸡胚畸形率增加 ；50Hz，0.5mT正弦磁场暴露可引起鼠胚胎细胞DNA双链断裂，卵裂速度明显下降 ， 0.4 mT工频磁场长时间辐照可以使人晶状体上皮细胞DNA 双链断裂增加 。但也有报道称，人血细胞暴露于50 Hz、l mT磁场中48 h，DNA无损伤 。目前多数的研究还局限于肿瘤和生殖方面的调查研究，而对神经系统研究的比较少，仅有一些工频电磁场对大鼠记忆力的影响 ，以及工频磁场能够造成大鼠脑组织的脂质过氧化，尤其是基底前脑和额皮质部位 的研究。 经过多年的研究发现极低频电磁场能通过诱导细胞膜受体的聚集、降低膜的流动性和导电性、改变膜的结构等干扰细胞信号超导 。实际上，在许多病理状态下，都有细胞膜势能的改变，膜的结构组织上出现的变化导致了细胞膜极性的翻转等。现阶段磁场生物效应没有明确的理论基础，很多对于此方面的原因的研究都处于假设阶段 。 现已发现许多脑部疾病与钾通道特性改变有关，研究工频电磁场对中枢神经细胞膜钾离子通道特性的影响，有可能为电磁场直接作用于脑组织引起某些脑部病变的机理起指导作用。鉴于电压门控K + 通道在调节神经细胞膜兴奋性及神经可塑性中起着关键作用，本文利用膜片钳实验技术，研究50Hz工频电磁场对小鼠皮层神经元瞬时外向钾通道特性的影响，为从细胞和分子水平探索50Hz工频电磁场的生物刺激效应开辟了一条新的道路，为人们研究极低频磁场对神经系统的影响提供依据。 2. 材料与方法 2.1. 材料 动物：昆明小鼠，鼠龄10～13天，雌雄不限，由中国医学科学院放射医学研究所提供。 试剂：链霉蛋白酶（Pronase），Merck公司产品。河豚毒素（TTX）、氯化镉（CdCl 2 ）、氯化四乙胺（TEA-Cl）、N-2-羟乙基哌嗪-N-2-乙磺酸（HEPES）、已二醇－双（2－氨基乙基）四乙酸（EGTA）、Na 2 ATP均为Sigma公司产品。其余为国产分析纯。 （1）人工脑脊液(ACSF, mmol/L)：NaCl 134，KCl 5，NaH 2 PO 4 1.5，MgSO 4 2，CaCl 2 2， NaHCO 3 25，Glucose 10，HEPES 10，pH7.4；使用前通氧气饱和。 （2）K通道标准细胞外液（mmol/L）：NaCl 130，KCl 5.4，CaCl 2 2，MgCl 2 1，Glucose 10，HEPES 10，pH7.3，使用前通氧气饱和； （3）K通道电极内液（mmol/L）：KCl 120，CaCl 2 1，HEPES 10，EGTA 10，Na 2 ATP 3，MgCl 2 2，pH7.2，经0.22滤膜过滤。 2.2. 小鼠大脑皮层神经元急性分离 取出生10天左右的昆明小鼠迅速断头取脑，置于4C人工脑脊液中，一分钟后将脑切成冠状切片，并继续切取皮层组织，厚度约为400左右，放入连续通95%O 2 +5%CO 2 混合气的人工脑脊液中，孵育50分钟。之后加入Pronase，其终浓度为0.36g / L，32C下消化15min。消化结束用人工脑脊液洗脑片3次，加入盛有人工脑脊液的离心管中，用4根口径渐小的Pasteur吸管轻轻吹打组织块，制成细胞悬液，静置5min后取上部细胞悬液，放入带有盖玻片的培养皿内，约15～20min后细胞贴壁。分离完整的皮层神经细胞显微镜下观察，形态呈锥体或椭圆形，顶树突和轴突完整，细胞表面光滑，颗粒均匀细腻，它可在6～8小时内保持良好的生理状态 。 2.3. 全细胞膜片钳记录和数据分析 在20～25C室温下，利用PC2C膜片钳放大器（华中科大仪博生命科学仪器有限公司，中国）进行全细胞膜片钳记录，实验参数的设置、数据采集和刺激方式的施加均通过PC2C膜片钳自带软件来控制，采样频率为100kHz。记录用玻璃微电极（中科院电子所生产）经05-E型程控玻璃微电极拉制仪两步拉制而成，充灌电极内液后，电极阻抗为2～5。当电极与细胞膜之间形成高阻封接（1G）后，将钳制电位调到-80mV，进行快电容补偿后，稍加负压破膜，使电极液与细胞内液相通，再进行慢电容和串联电阻补偿，串联电阻补偿为60%～80%。 实验所用刺激装置由实验室自行研制，由自制圆形线圈外接交流稳压电源的形式产生2mT、50Hz磁场，通过改变线圈中电流的大小来改变线圈中心磁场的大小。先将小鼠的皮层神经细胞分离和贴壁，而后再将得到活性状态较好的细胞放置于工频电磁场当中，刺激后在进行膜片钳试验，最后将得到的数据和正常的进行对比研究，刺激过程如图1所示。 图 1 工频电磁场刺激示意图 Fig. 1 Schematic diagram of pulsating magnetic fields irradiation 实验结果分析采用Pclamp软件和Origin7.5统计软件完成，分析结果用MeanSD表示，脉冲磁场刺激前后差异的显著性用单因数方差分析和检验进行分析，P0.05表示有统计学差异。 3. 结果 3.1. 瞬时外向钾通道电流(I A )的记录 采用上述标准细胞外液和电极内液，且在外液中加入1 TTX 、0.1的CdCl 2 和20的TEA-Cl，记录皮层神经细胞膜上外向钾电流。置钳制电位于-80mV，给予脉冲幅度为-60mV～+50mV，脉冲宽度60ms，步幅+10mV的去极化脉冲刺激电压(图2A)，由于刺激频率与电流的强度大小没有直接关系，因此此次实验采用统一的刺激频率为0.25Hz，对得到的数据进行处理。该激活的外向电流即为快速激活和失活的瞬时外向钾电流I A (图2B)。 (A) (B) (C) 图2(A)刺激脉冲(B)记录的IA(C)曝磁后的IA Fig. 2 Transient outward potassium current traces (A) Depolarizing steps (B) Transient outward potassium current traces （ C ） Transient outward potassium current traces after magnetic fields exposure 考察正常皮层神经细胞I A 电流随时间变化的特点。给予图2A所示的去极化脉冲刺激，分别在1~6min记录不同时间的I A ，可知I A 在4min基本达到稳定。本试验分别采用加刺激与并未加刺激细胞第四分钟的I A 电流进行比较。 3.2. 工频电磁场刺激对I A 时间依赖性的影响 由于钾通道具有衰减（Rundown）现象，需要进行时间依赖性考察。给予与3.1相同的去极化脉冲刺激，分别对磁场照射15min和30min的I A 进行记录，已知I A 在4min基本达到稳定，数据记录应该从此时刻开始进行。为给予不同阶梯去极化脉冲刺激，经磁场作用15min和30min后的I A 电流密度的曲线。由实验结果可知：细胞经过曝磁后，I A 受到明显的抑制，对照组的最大电流密度为205.5326.95pA/pF (n=9, P0.05)，15min照射组最大电流密度为81.689.15pA/pF(n=9, P0.05) ，30min曝磁组的最大电流密度为43.575.59pA/pF(n=9, P0.05)。 图 3I A 随时间变化 曲线 Fig.3Effects of magnetic field irradiation on transient outward potassium currents in different irradiating time. Activation potential of transient outward potassium channel began to shift towards more negative potentials after irradiating for 15 min and 30min ( n =9) 3.3. 工频电磁场对瞬时外向钾电流 I - V 曲线的影响 给予同3.1中相同的刺激方式，将未加刺激和加工频电磁场刺激30min后得到的瞬时外向钾电流数据加以比较，以不同膜电位（去极化刺激电位）为横轴，该膜电位下激活的I A 电流密度值（电流/膜电容）为纵轴，绘制通道电流的曲线（图4）。对照组和曝磁组的最大激活电流密度分别为 205.53 26.95pA/pF ，43.57 5.59pA/pF 。由 I - V 曲线可知，经检验，对照组和工频电磁场刺激组I A 在统计学上具有显著性差异（n=9, P0.05）。 图 4 对照组、曝磁组 I A 的 曲线 Fig.4 Transient outward potassium currents difference between the control and magnetic field irradiation 3.4. 工频电磁场对I A 稳态激活特性的影响 置钳制电位-80mV，预置-120mV超极化条件刺激200ms，然后给予脉冲幅度从-60mV～+50mV，脉冲宽度60ms，步幅+10mV的去极化测试脉冲电压刺激，引出一系列瞬时外向钾电流，以第四分钟纪录的瞬时外向钾电流作为对照。以本文前述方法磁场照射细胞，照射时间30min，再次记录上述电流，利用公式将电流值转换成电导值，其中 G 为电导、为测试膜电位，为翻转电位，为不同膜电位下测定的电流峰值。以电导值与最大电导值的比值对应膜电位分别绘制工频电磁场作用前后I K 的稳态激活曲线（图5）。所得曲线可以用玻尔兹曼（Boltzmann）方程拟和，其中为半数激活电压， 为曲线的斜率因子。由图 5可以看出对照组与工频电磁场组激活曲线均呈 S型，并由此计算出对照组和磁场照射组瞬时外向钾通道的半数激活电压 分别为19.962.87mV和8.121.67mV（n＝9, P0.05），斜率因子分别为22.282.09和19.771.71mV（n=9,P0.05）。由此可知，工频磁场作用可明显改变I A 的激活特性，使激活曲线向左移动，并改变其斜率因子。 图5 对照组、工频磁场照射组I A 的激活曲线 Fig. 5 Effects of magnetic field irradiating on steady-state activation kinetics of I A . 4. 结论 实验结果表明，2.0mT、50Hz工频磁场作用，使小鼠皮层神经细胞膜瞬时外向钾通道电流I A 受到一定程度的抑制，且这种抑制作用呈现时间依赖性、电压依赖性。结果还表明，工频磁场的作用可使I A 的激活曲线显著地左移，且改变曲线的斜率因子。说明工频磁场作用皮层神经元，引起神经细胞膜瞬时外向钾离子通道I A 的激活过程受到抑制，使得动作电位复极化早期电压依赖性钾通道的开放延迟且关闭加快，从而使得 K + 外流减少。这一结果为各种家用电器对人体影响及磁疗产品对真实的治疗疗效提供实验参考。 电压门控离子通道是神经元电活动的分子基础，它参与初级生物信息传导，并在神经动作电位的产生、突触传递和其它重要的生理功能中起着重要作用。电压门控 Na + 通道决定了动作电位的产生，Ca 2+ 通道是再生电位产生的基础，而K + 通道在调节神经细胞膜兴奋性、神经可塑性及 在神经元的信号调控过程中起主要作用，同时也是某些神经毒素和药物作用的靶点。通过抑制瞬时外向 K+ 通道激活，使胞内钙浓度增加，对受损神经元起保护作用。 瞬时外向钾电流I A 是动作电位复极化早期外向电流的主要成分，主要调节静息膜电位，减慢去极化的速度，决定动作电位产生的频率。工频磁场作用改变小鼠皮层神经元瞬时外向钾通道电流的稳态激活特性，从而会影响神经元动作电位的形成和发放，最终调节神经元的生理功能。 磁场的生物刺激作用机制和作用靶点目前尚不明确，仅限于一些假说，而低频电磁场对有机体的作用更是一个非线性、瞬态的复杂过程。本实验从细胞膜电压门控钾离子通道角度研究工频磁场这种极低频磁场的生物刺激作用。磁场作为一种物理因素，对运动的带电物质有洛伦兹力的作用，影响细胞膜的离子通透性和膜两侧的电位，引起机体内环境平衡，从而影响带电物质的转移过程，产生一些生物效应。本实验结果提示工频磁场的生物刺激作用与细胞膜离子通道特性及通道构形变化有关，但仍需进一步从分子生物学及细胞信号转导方面进行分子层面的理论和实验验证。 参考文献 刘志华，时丽冉. 电磁辐射对人体健康的影响 ，生物学通报，2006,41(3):30-31 LIU Z H, SHI L R. 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Research on characteristics of neuron potassium channel under low laser irradiation , ACTA PHYSICA SINICA, 2007,56(4):2448-2454.(in Chinese) 乔晓艳，李刚，贺秉军. 弱激光对大鼠海马神经元钠通道特性的影响 , 生物化学与生物物理进展, 2006,33(2):178-182. QIAO X Y, LI G, HE B J. Effects of low level laser irradiation on properties of sodium channel in rat hippocampal neurons , Progress in Biochemistry and Biophysics , 2006, 33(2): 178 - 182. (in Chinese)
脉冲磁场对皮层神经元瞬时外向钾电流 影响的初步实验研究 1. 引言 现代科学的发展已经表明，任何空间都存在着或低或高的磁场，这些生物磁场及其变化与生物的生命活动、生理状态密切相关。随着生物磁技术的发展，有关磁场作用与生物学效应的研究，取得了积极的成果，不仅丰富了磁场疗法的基础理论，而且推动了磁场疗法的发展与深入，各类磁疗在医学中的基础和临床应用研究越来越广泛。现代科技的发展使人们越来越多的暴露在各种各样的磁场中，磁场对人体正常的机理有着何种影响，及其影响机理如何至今未明 。 低频脉冲磁场在促进骨折愈合 、改善血流变 、预防静脉血栓、脊髓损伤及脑创伤 等方面不断有研究报道；同时射频电磁场可对人体造成多种伤害也多见报道。在神经系统主要表现为神经衰弱，同时伴有植物神经功能失调的征候 。也可影响内分泌功能。微波可使精子数量减少，活动能力降低，甚至可发生暂时性不育。妇女在妊娠早期受微波照射可引起流产，分娩后可引起乳汁分泌量减少。人们又可以利用电磁场的生物学效应来治疗某些疾病，如促进骨折愈合用做肿瘤的辅助治疗等脉冲电磁场刺激对周围神经的再生有一定促进作用 。 经过多年的研究磁场对于细胞膜有着特殊的影响 ，特别是磁场的脉冲作用 ，能够改变细胞膜两侧的离子分布，从而在某些创伤或是变性的组织产生的炎症反映中表现出治疗效应。磁场对生物膜效应有以下几个方面：磁场对于许多细胞内的酶系统有影响、它们影响了抗原和抗体的关系、它们使得细胞膜通透性发生了改变，从而改变了膜两侧离子平衡；实际上，在许多病理状态下，都有细胞膜势能的改变，膜的结构组织上出现的变化导致了细胞膜极性的翻转等。现阶段磁场生物效应没有明确的理论基础，很多对于此方面的原因的研究都处于假设阶段，因此对于电磁作用生物组织治疗机理的研究还在逐步进行中 。 2. 材料与方法 2.1. 材料 动物：昆明小鼠，鼠龄10～14天，雌雄不限，天津医科大学动物实验中心提供。 试剂：链霉蛋白酶（Pronase），Merck公司产品。河豚毒素（TTX）、氯化镉（CdCl 2 ）、氯化四乙胺（TEA-Cl）、N-2-羟乙基哌嗪-N-2-乙磺酸（HEPES）、已二醇－双（2－氨基乙基）四乙酸（EGTA）、Na 2 ATP均为Sigma公司产品。其余为国产分析纯。 （1）人工脑脊液(ACSF, mmol/L)：NaCl 134，KCl 5，NaH 2 PO 4 1.5，MgSO 4 2，CaCl 2 2， NaHCO 3 25，Glucose 10，HEPES 10，pH7.4；使用前通氧气饱和。 （2）K通道标准细胞外液（mmol/L）：NaCl 130，KCl 5.4，CaCl 2 2，MgCl 2 1，Glucose 10，HEPES 10，pH7.3，使用前通氧气饱和； （3）K通道电极内液（mmol/L）：KCl 120，CaCl 2 1，HEPES 10，EGTA 10，Na 2 ATP 3，MgCl 2 2，pH7.2，经0.22滤膜过滤。 2.2. 小鼠大脑皮层神经元急性分离 取出生10天左右的昆明小鼠迅速断头取脑，置于4C人工脑脊液中，一分钟后将脑切成冠状切片，并继续切取皮层组织，厚度约为400左右，放入连续通95%O 2 +5%CO 2 混合气的人工脑脊液中，孵育50分钟。之后加入Pronase，其终浓度为0.36g / L，32C下消化15min。消化结束用 人工脑脊液洗脑片3次，加入盛有人工脑脊 液的离心管中，用4根口径渐小的Pasteur吸管轻轻吹打组织块，制成细胞悬液，静置5min后取上部细胞悬液，放入带有盖玻片的培养皿内，约15～20min后细胞贴壁。分离完整的皮层神经细胞显微镜下观察，形态呈锥体或椭圆形，顶树突和轴突完整，细胞表面光滑，颗粒均匀细腻，它可在6～8小时内保持良好的生理状态 。 2.3. 全细胞膜片钳记录和数据分析 在25C室温下，利用PC2C膜片钳放大器（华中科大）进行全细胞膜片钳记录，实验参数的设置、数据采集和刺激方式的施加均通过软件来控制，采样频率为100kHz。记录用玻璃微电极经两步拉制而成，充灌电极内液后，电极阻抗为1.5～3。当电极与细胞膜之间形成高阻封接（1G）后，将钳制电位调到-80mV，进行快电容补偿后，稍加负压破膜，使电极液与细胞内液相通，再进行慢电容和串联电阻补偿。 实验所用刺激装置由实验室自行研制，先将小鼠的皮层神经细胞分离和贴壁，而后再将得到活性状态较好的细胞放置于脉冲磁场当中，刺激后在进行膜片钳试验，最后将得到的数据和正常的进行对比研究，刺激过程如图1所示。 图 1 脉冲磁场刺激示意图 Fig. 1 Schematic diagram of pulsating magnetic fields irradiation 实验结果分析采用Pclamp软件和Origin7.5统计软件完成，分析结果用MeanSD表示，脉冲磁场刺激前后差异的显著性用单因 数方差分析和检验进行分析，P0.05表示有统计学差异。 3. 结果 3.1. 瞬时外向钾通道电流(I A )的记录 采用上述标准细胞外液和电极内液，且在外液中加入1 TTX 、0.1的CdCl 2 和20的TEA-Cl，记录皮层神经细胞膜上外向钾电流。置钳制电位于-80mV，给予脉冲幅度为-60mV～+50mV，脉冲宽度60ms，步幅+10mV的去极化脉冲刺激电压(图2A)，由于刺激频率与电流的强度大小没有直接关系 ，因此此次实验采用统一的刺激频率为0.025Hz，对得到的数据进行处理。该激活的外向电流即为快速激活和失活的瞬时外向钾电流I A (图2B)。 (A) (B) (C) 图 2 (A) 刺激脉冲 (B) 记录的 I A (C) 曝磁后的 I A Fig. 2 Transient outward potassium current traces (A) Depolarizing steps (B) Transient outward potassium current traces （ C ） Transient outward potassium current traces after magnetic fields exposure 考察正常皮层神经细胞I A 电流随时间变化的特点。给予图2A所示的去极化脉冲刺激，分别在1~6min记录不同时间的I A ，可知I A 在4min基本达到稳定。本试验分别采用加刺激与并未加刺激细胞第四分钟的I A 电流进行比较。 3.2. 脉冲磁场刺激对 I A 时间依赖性的影响 给予与3.1相同的去极化脉冲刺激，分别对磁场照射25min和45min的I A 进行记录，已知I A 在4min基本达到稳定，数据记录应该从此时刻开始进行。为给予不同阶梯去极化脉冲刺激，经磁场作用25min和45min后的I A 电流密度的曲线。由实验结果可知：细胞经过曝磁后，I A 受到明显的抑制，对照组的最大电流密度为213.8041.65pA/pF(n=9, P0.05)，25min照射组最大电流密度为70.2421.92pA/pF(n=6, P0.05) ，45min曝磁组的最大电流密度为49.2810.91pA/pF(n=6, P0.05)。 图 3I A 随时间变化 I-V 曲线 Fig.3Effects of magnetic field irradiation on transient outward potassium currents in different irradiating time. Activation potential of transient outward potassium channel began to shift towards more negative potentials after irradiating for 25 min and 45min ( n =6). 3.3. 脉冲磁场对瞬时外向钾电流 曲线的影响 将未加刺激和加磁场刺激后得到的瞬时外向钾电流数据加以比较，其结果如图4所示。 以不同膜电位（去极化刺激电位）为横轴，该膜电位下激活的I A 电流密度值（电流/膜电容）为纵轴，绘制通道电流的曲线（图4）。对照组和曝磁组的最大激活电流密度分别为213.8041.65pA/pF、67.4622.34pA/pF。由曲线可知，脉冲磁场可以抑制I A 。并且经检验，对照组和脉冲磁场刺激组I A 在统计学上具有显著性差异（n=10, P0.05）。 图 4 对照组、曝磁组 I A 的 曲线 Fig.4 Transient outward potassium currents difference between the control and magnetic field irradiation 3.4. 脉冲磁场对I A 稳态激活特性的影响 给予同3.1中相同的刺激方式，以第四分钟纪录的瞬时外向钾电流作为对照。利用公式将电流值转换成电导值，其中 G 为电导、为测试膜电位，为翻转电位，为不同膜电位下测定的电流峰值。以电导值与最大电导值的比值对应膜电位分别绘制脉冲磁场作用前后I A 的稳态激活曲线（图5）。所得曲线可以用Boltzmann方程拟和，其中为半数激活电压，为曲线的斜率因子。由图5可以看出对照组与脉冲磁场组激活曲线均呈S型，并由此计算出对照组和曝磁组瞬时外向钾通道的半数激活电压分别为13.252.22mV和30.984.11mV（n＝6, P0.05），斜率因子分别为24.002.05mV和23.302.13mV（n=6,P0.05）。由此可知，脉冲磁场作用可明显改变I A 的激活特性，使激活曲线向右移动，并不改变其斜率因子。 图5 对照组、脉冲磁场照射组I A 的激活曲线 Fig. 5 Effects of magnetic field irradiating on steady-state activation kinetics of I A . Currents were elicited with a series of 160 ms step pulses from 60 mV to 50 mV (10 mV increment for each step). Each point represents meanS.D. (n=6). 4. 结论 实验结果表明，频率为15Hz，强度为1.4mT,占空比位50%的脉冲磁场的作用，使小鼠皮层神经细胞膜瞬时外向钾通道电流I A 受到一定的抑制。结果还表明，脉冲磁场的作用可使I A 的激活曲线显著地右移，但其并不改变曲线的斜率因子。据文献 ，神经细胞膜瞬时外向钾离子通道I A 的激活过程受到抑制，会使得电压依赖性钾通道的开放延迟,抑制I A 的激活过程而调节神经细胞的静息电位和兴奋性，延缓神经细胞的去极化过程，加速动作电位的产生。因此可知脉冲磁场作用皮层神经细胞可以改变其瞬时外向钾通道特性，从而影响动作电位的形成和发放频率，调节神经元的生理功能,有利于受损神经元的恢复和再生。 低频脉冲磁场对有机体的作用是一个非线性、瞬态的过程，主要集中在生物膜上。在中枢神经系统，由于对获取的信号存在放大机制，即便采用低频低能脉冲磁场，在毫微秒的瞬间使膜电位发生毫伏量级的细微改变，也可使神经细胞膜电位发生意义深远的变化。神经元的快速信号获取，是典型敏感的膜离子通道关闭或开往，控制膜内外的钠、钾、钙等离子转运。无论是膜两侧离子浓度比之的变化还是电荷穿越质膜迁移所携带的信息，都会改变细胞自身的生理和生化状态。但其具体影响的机理则需要进一步的工作去研究。 参考文献 : MIYAKOSHI.J. Biological responses to extremely low-frequency electromagnetic fields , Journal of Dermatological Science Supplement , 2006,2(1):S23-S30. 徐巧玲，路丽华，罗二平，等. 低强度脉冲电磁场对大鼠骨密度及骨形态计量学的影响 , 第四军医大学学报, 2004,25(21):2004-2006. XU Q L,LU L H,LUO E P, et al .. 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标签: 神经元
