更改

因此，电压门控离子通道在膜电位处于某些水平时倾向于打开，在其他水平时倾向于关闭。然而，膜电位和离子通道的状态之间在大多数情况下是一种概率关系，并且存在时间延迟。离子通道在不可预测的时间在不同构象之间切换：膜电位决定状态切换速率和单位时间每种切换类型的概率。

因此，电压门控离子通道在膜电位处于某些水平时倾向于打开，在其他水平时倾向于关闭。然而，膜电位和离子通道的状态之间在大多数情况下是一种概率关系，并且存在时间延迟。离子通道在不可预测的时间在不同构象之间切换：膜电位决定状态切换速率和单位时间每种切换类型的概率。

[[File:Blausen 0011 ActionPotential Nerve.png|thumb|300px|left|Action potential propagation along an axon沿着轴突的动作电位传导|链接=Special:FilePath/Blausen_0011_ActionPotential_Nerve.png]]

[[File:Blausen 0011 ActionPotential Nerve.png|thumb|300px|left|动作电位沿着轴突传导|链接=Special:FilePath/Blausen_0011_ActionPotential_Nerve.png]]

电压门控离子通道能够产生动作电位，是因为它们能够产生正反馈回路：膜电位控制离子通道的状态，而离子通道的状态控制膜电位。因此，在某些情况下，膜电位的上升会导致离子通道打开，又导致膜电位的进一步上升。当这种正反馈循环（Hodgkin 循环）爆发性地进行时，就会产生动作电位。电压门控离子通道的生物物理特性决定了动作电位的时间和幅度轨迹。存在几种能产生动作电位所必需的正反馈回路的离子通道。电压门控性钠通道负责神经传导的快速动作电位。肌细胞和某些类型的神经元的稍慢的动作电位是由电压门控钙通道产生的。每种类型都有多种变体，具有不同的电压灵敏度和不同的时间动力学。

电压门控离子通道能够产生动作电位，是因为它们能够产生正反馈回路：膜电位控制离子通道的状态，而离子通道的状态控制膜电位。因此，在某些情况下，膜电位的上升会导致离子通道打开，又导致膜电位的进一步上升。当这种正反馈循环（Hodgkin 循环）爆发性地进行时，就会产生动作电位。电压门控离子通道的生物物理特性决定了动作电位的时间和幅度轨迹。存在几种能产生动作电位所必需的正反馈回路的离子通道。电压门控性钠通道负责神经传导的快速动作电位。肌细胞和某些类型的神经元的稍慢的动作电位是由电压门控钙通道产生的。每种类型都有多种变体，具有不同的电压灵敏度和不同的时间动力学。

[[Category:Action potentials]]

[[Category:Action potentials]]

[[Category:待整理页面]]

[[Category:待整理页面]]

Given its conservation throughout evolution, the action potential seems to confer evolutionary advantages. One function of action potentials is rapid, long-range signaling within the organism; the conduction velocity can exceed 110 m/s, which is one-third the [[speed of sound]]. For comparison, a hormone molecule carried in the bloodstream moves at roughly 8 m/s in large arteries. Part of this function is the tight coordination of mechanical events, such as the contraction of the heart. A second function is the computation associated with its generation. Being an all-or-none signal that does not decay with transmission distance, the action potential has similar advantages to [[digital electronics]]. The integration of various dendritic signals at the axon hillock and its thresholding to form a complex train of action potentials is another form of computation, one that has been exploited biologically to form [[central pattern generator]]s and mimicked in [[artificial neural network]]s.

鉴于动作电位在整个进化过程中的保守性，它似乎赋予生物某些进化优势。动作电位的一个功能是在生物体内进行快速的远距离信号传导，传导速率可逾 110 米/秒，即声速的三分之一。相比之下，血液携带的激素分子在大动脉中的运动速度约为 8 米/秒。一个功能是对力学活动，例如心脏收缩，进行严格的协调。第二个功能是动作电位的产生相关的计算。动作电位作为一种全或无信号，不随传输距离衰减，与数字电子技术具有相似的优点。各种树突信号在轴丘的整合以及通过域值二值化（thresholding）产生动作电位的复杂序列是另一种形式的计算，在生物中用来形成中央模式发生器（central pattern generator），为人工神经网络带来启示。

目前认为生活在大约 40 亿年前的原核/真核生物的共同祖先，就已具有电压门控通道。在之后的某个时候，被转而用来提供一个通讯机制。即使现代的单细胞细菌也可以利用动作电位与生物膜（biofilm）中的其他细菌进行通讯。<ref name=":19">{{cite journal | vauthors = Kristan WB | title = Early evolution of neurons | journal = Current Biology | volume = 26 | issue = 20 | pages = R949–R954 | date = October 2016 | pmid = 27780067 | doi = 10.1016/j.cub.2016.05.030 | doi-access = free }}</ref>

 

The common prokaryotic/eukaryotic ancestor, which lived perhaps four billion years ago, is believed to have had voltage-gated channels. This functionality was likely, at some later point, cross-purposed to provide a communication mechanism. Even modern single-celled bacteria can utilize action potentials to communicate with other bacteria in the same biofilm.<ref name=":19">{{cite journal | vauthors = Kristan WB | title = Early evolution of neurons | journal = Current Biology | volume = 26 | issue = 20 | pages = R949–R954 | date = October 2016 | pmid = 27780067 | doi = 10.1016/j.cub.2016.05.030 | doi-access = free }}</ref>

 

生活在大约 40 亿年前的原核/真核生物的共同祖先，被认为具有电压门控通道。在以后的某个时候，这个功能可能会被用来提供一个通信机制。即使是现代的单细胞细菌也可以利用动作电位与生物膜（biofilm）中的其他细菌进行交流。<ref name=":19" />

==实验方法==

==实验方法==

[[Image:Loligo forbesii.jpg|thumb|right|250px|Giant axons of the longfin inshore squid （''[[Doryteuthis pealeii]]''） were [[Marine Biological Laboratory#Neuroscience, neurobiology, and sensory physiology|crucial for scientists]] to understand the action potential.<ref>{{cite book |url=https://books.google.com/books?id=SDi2BQAAQBAJ |title=The Brain, the Nervous System, and Their Diseases |first=Jennifer L. |last=Hellier | name-list-style = vanc |year=2014 |pages=532 |publisher=ABC-Clio |isbn=9781610693387}}</ref>长鳍近海鱿鱼（Doryteuthis pealeii）的巨型轴突对于科学家了解动作电位至关重要。[注1]|链接=Special:FilePath/Loligo_forbesii.jpg]]

[[Image:Loligo forbesii.jpg|thumb|right|250px|长鳍近海的枪乌贼（''Doryteuthis pealeii''）的巨大轴突对于科学家了解动作电位至关重要。<ref>{{cite book |url=https://books.google.com/books?id=SDi2BQAAQBAJ |title=The Brain, the Nervous System, and Their Diseases |first=Jennifer L. |last=Hellier | name-list-style = vanc |year=2014 |pages=532 |publisher=ABC-Clio |isbn=9781610693387}}</ref>|链接=Special:FilePath/Loligo_forbesii.jpg]]

 

 

 

 

The second problem was addressed with the crucial development of the [[voltage clamp]],<ref name="cole_1949" group="lower-alpha">{{cite journal | vauthors = Cole KS | year = 1949 | title = Dynamic electrical characteristics of the squid axon membrane | journal = Arch. Sci. Physiol. | volume = 3 | pages = 253–8| author-link = Kenneth Stewart Cole }}</ref> which permitted experimenters to study the ionic currents underlying an action potential in isolation, and eliminated a key source of [[electronic noise]], the current ''I_C'' associated with the [[capacitance]] ''C'' of the membrane.{{sfn|Junge|1981|pp=63–82}} Since the current equals ''C'' times the rate of change of the transmembrane voltage ''V_m'', the solution was to design a circuit that kept ''V_m'' fixed （zero rate of change） regardless of the currents flowing across the membrane. Thus, the current required to keep ''V_m'' at a fixed value is a direct reflection of the current flowing through the membrane. Other electronic advances included the use of [[Faraday cage]]s and electronics with high [[input impedance]], so that the measurement itself did not affect the voltage being measured.{{sfn|Kettenmann|Grantyn|1992}}

研究动作电位需要开发新的实验方法。在 1955 年之前初步工作主要是由 [[Alan Lloyd Hodgkin]] 和 Andrew Fielding Huxley 进行的，他们因神经传导的离子机制的工作，与  [[John Carew Eccles]] 一起被授予 1963 年的诺贝尔生理学或医学奖。这些工作围绕三个目标：从单个神经元或轴突中分离出信号，开发快速、灵敏的电子设备，以及缩小电极以记录单个细胞里的电位。

第二个问题由于电压钳<ref name="cole_1949" group="lower-alpha" /> 的重要发展解决，让实验人员可以研究单个实验者研究单独的动作电位的离子电流，并消除了电子噪声的主要根源——与膜电容 ''C'' 关联的电流 ''I_C''。由于电流等于''C''  c 乘以跨膜电压  ''V_m''  的变化率，所以解决方案是设计一个电路，使  ''V_m''  保持固定（零变化率），而不管跨膜电流的变化。因此，使  ''V_m''  Vm 保持在一个固定值所需的电流是流过薄膜的电流的直接反射。其他电子方面的进步包括使用法拉第笼和具有高输入阻抗的电子器件，这样测量本身就不会影响被测量的电压。

第一个问题通过研究枪乌贼（''[[Loligo forbesii]]'' 和 ''[[Doryteuthis pealeii]]'', 当时被归类为 ''Loligo pealeii''）神经元中发现的巨大轴突得以解决。<ref name="keynes_1989" group="lower-alpha">{{cite journal | vauthors = Keynes RD | title = The role of giant axons in studies of the nerve impulse | journal = BioEssays | volume = 10 | issue = 2–3 | pages = 90–3 | year = 1989 | pmid = 2541698 | doi = 10.1002/bies.950100213 }}</ref> 这些轴突直径很大（约 1 毫米，比一个典型的神经元大 100 倍），肉眼可见，因此很容易提取和操作。<ref name="hodgkin_1952" group="lower-alpha" /><ref name="Meunier" group="lower-alpha">{{cite journal | vauthors = Meunier C, Segev I | title = Playing the devil's advocate: is the Hodgkin-Huxley model useful? | journal = Trends in Neurosciences | volume = 25 | issue = 11 | pages = 558–63 | date = November 2002 | pmid = 12392930 | doi = 10.1016/S0166-2236(02)02278-6 | s2cid = 1355280 }}</ref> 不过，它们并不代表所有的兴奋性细胞，人们也研究了多种其他的动作电位系统。

The third problem, that of obtaining electrodes small enough to record voltages within a single axon without perturbing it, was solved in 1949 with the invention of the glass micropipette electrode,<ref name="ling_1949" group="lower-alpha">{{cite journal | vauthors = Ling G, Gerard RW | title = The normal membrane potential of frog sartorius fibers | journal = Journal of Cellular and Comparative Physiology | volume = 34 | issue = 3 | pages = 383–96 | date = December 1949 | pmid = 15410483 | doi = 10.1002/jcp.1030340304 }}</ref> which was quickly adopted by other researchers.<ref name="nastuk_1950" group="lower-alpha">{{cite journal | vauthors = Nastuk WL, Hodgkin A | year = 1950 | title = The electrical activity of single muscle fibers | journal = Journal of Cellular and Comparative Physiology | volume = 35 | pages = 39–73 | doi = 10.1002/jcp.1030350105 }}</ref><ref name="brock_1952" group="lower-alpha">{{cite journal | vauthors = Brock LG, Coombs JS, Eccles JC | title = The recording of potentials from motoneurones with an intracellular electrode | journal = The Journal of Physiology | volume = 117 | issue = 4 | pages = 431–60 | date = August 1952 | pmid = 12991232 | pmc = 1392415 | doi = 10.1113/jphysiol.1952.sp004759 }}</ref> Refinements of this method are able to produce electrode tips that are as fine as 100 [[Ångström|Å]] （10 [[nanometre|nm]]）, which also confers high input impedance.<ref name=":20">Snell, FM in {{harvnb|Lavallée|Schanne|Hébert|1969|loc=''Some Electrical Properties of Fine-Tipped Pipette Microelectrodes''.}}</ref> Action potentials may also be recorded with small metal electrodes placed just next to a neuron, with [[neurochip]]s containing [[EOSFET]]s, or optically with dyes that are [[Calcium imaging|sensitive to Ca²⁺]] or to voltage.<ref name="dyes" group="lower-alpha">{{cite journal | vauthors = Ross WN, Salzberg BM, Cohen LB, Davila HV | title = A large change in dye absorption during the action potential | journal = Biophysical Journal | volume = 14 | issue = 12 | pages = 983–6 | date = December 1974 | pmid = 4429774 | pmc = 1334592 | doi = 10.1016/S0006-3495(74)85963-1 | bibcode = 1974BpJ....14..983R }}<br />* {{cite journal | vauthors = Grynkiewicz G, Poenie M, Tsien RY | title = A new generation of Ca2+ indicators with greatly improved fluorescence properties | journal = The Journal of Biological Chemistry | volume = 260 | issue = 6 | pages = 3440–50 | date = March 1985 | doi = 10.1016/S0021-9258(19)83641-4 | pmid = 3838314 | doi-access = free }}</ref>

第二个问题随着电压钳<ref name="cole_1949" group="lower-alpha">{{cite journal | vauthors = Cole KS | year = 1949 | title = Dynamic electrical characteristics of the squid axon membrane | journal = Arch. Sci. Physiol. | volume = 3 | pages = 253–8| author-link = Kenneth Stewart Cole }}</ref> 关键性的开发得以解决，让实验者可以对动作电位的离子电流进行单独研究，并消除了电子噪声的主要来源——与膜电容 ''C'' 关联的电流 ''I_C''。因为电流等于''C'' 乘以跨膜电压 ''V_m'' 的变化率，所以解决方案就是设计一个电路，让 ''V_m'' 保持固定（零变化率），不管跨膜电流的变化。因此，使 ''V_m'' 保持固定所需的电流是流过膜的电流直接取反。电子设备的其他进步包括法拉第笼（Faraday cages）和具有高输入阻抗的电子器件的使用，这样测量本身就不会影响被测量的电位。

第三个问题是如何获得足够小的电极来记录单个轴突内的电压而不对其造成干扰，这个问题在1949年由于玻璃微电极<ref name="ling_1949" group="lower-alpha" /> 的发明而得到解决，并且很快被其他研究人员采用。<ref name="nastuk_1950" group="lower-alpha" /><ref name="brock_1952" group="lower-alpha" /> 这种方法的改进可以生产出 [[Ångström|Å]] （10 [[nanometre|nm]]）100 纳米的电极尖端，同时也提供了高的输入阻抗。<ref name=":20" /> 动作电位也可以用放置在神经元旁的小金属电极记录下来，用含有 [[EOSFET]]s 的神经芯片，或者用对 Ca²⁺ 或电压敏感的染料记录下来。<ref name="dyes" group="lower-alpha" />  

[[Image:Single channel.png|thumb|left|As revealed by a [[patch clamp]] electrode, an [[ion channel]] has two states: open （high conductance） and closed （low conductance）.

第三个问题是如何获得足够小的电极来记录单个轴突内的电位而不对其造成干扰，这个问题在 1949 年因玻璃微电极的发明而得以解决。<ref name="ling_1949" group="lower-alpha">{{cite journal | vauthors = Ling G, Gerard RW | title = The normal membrane potential of frog sartorius fibers | journal = Journal of Cellular and Comparative Physiology | volume = 34 | issue = 3 | pages = 383–96 | date = December 1949 | pmid = 15410483 | doi = 10.1002/jcp.1030340304 }}</ref> 玻璃电极很快被其他研究人员所采用。<ref name="nastuk_1950" group="lower-alpha">{{cite journal | vauthors = Nastuk WL, Hodgkin A | year = 1950 | title = The electrical activity of single muscle fibers | journal = Journal of Cellular and Comparative Physiology | volume = 35 | pages = 39–73 | doi = 10.1002/jcp.1030350105 }}</ref><ref name="brock_1952" group="lower-alpha">{{cite journal | vauthors = Brock LG, Coombs JS, Eccles JC | title = The recording of potentials from motoneurones with an intracellular electrode | journal = The Journal of Physiology | volume = 117 | issue = 4 | pages = 431–60 | date = August 1952 | pmid = 12991232 | pmc = 1392415 | doi = 10.1113/jphysiol.1952.sp004759 }}</ref> 这种方法改进后可以生产出细到 100 Å（10 nm）且有高输入阻抗的电极端部。<ref name=":20">Snell, FM in {{harvnb|Lavallée|Schanne|Hébert|1969|loc=''Some Electrical Properties of Fine-Tipped Pipette Microelectrodes''.}}</ref> 动作电位也可用置于神经元附近的小金属电极、或电解质氧化物半导体场效应晶体管（EOSFET）的神经芯片（neurochip）进行记录，或利用 Ca²⁺ 或电压敏感的染料进行光学记录。<ref name="dyes" group="lower-alpha">{{cite journal | vauthors = Ross WN, Salzberg BM, Cohen LB, Davila HV | title = A large change in dye absorption during the action potential | journal = Biophysical Journal | volume = 14 | issue = 12 | pages = 983–6 | date = December 1974 | pmid = 4429774 | pmc = 1334592 | doi = 10.1016/S0006-3495(74)85963-1 | bibcode = 1974BpJ....14..983R }}<br />* {{cite journal | vauthors = Grynkiewicz G, Poenie M, Tsien RY | title = A new generation of Ca2+ indicators with greatly improved fluorescence properties | journal = The Journal of Biological Chemistry | volume = 260 | issue = 6 | pages = 3440–50 | date = March 1985 | doi = 10.1016/S0021-9258(19)83641-4 | pmid = 3838314 | doi-access = free }}</ref>[[Image:Single channel.png|thumb|left|电压钳电极揭示了，离子通道有两个状态：开放（高电导）和关闭（低电导）。|链接=Special:FilePath/Single_channel.png]]

 

电压钳电极揭示了，离子通道有两个状态：开放（高电导）和关闭（低电导）。|链接=Special:FilePath/Single_channel.png]]

玻璃微电极测量的是很多离子通道的总电流，在 1970 年代 [[Erwin Neher]] 和 [[Bert Sakmann]] 发明的膜片钳（patch clamp）使研究单个离子通道的电学性质成为可能。两位科学家因此被授予 1991 年诺贝尔生理学或医学奖科学奖。<ref name="Nobel_1991" group="lower-Greek">{{cite press release | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1991/press.html | title = The Nobel Prize in Physiology or Medicine 1991 | publisher = The Royal Swedish Academy of Science | year = 1991 | access-date = 2010-02-21 | url-status = live | archive-url = https://web.archive.org/web/20100324031907/http://nobelprize.org/nobel_prizes/medicine/laureates/1991/press.html | archive-date = 24 March 2010 | df = dmy-all }}</ref> 膜片钳技术证实了离子通道具有分立的电导状态，如打开状态、关闭状态和失活状态。

玻璃微电极测量的是很多离子通道的总电流，在 1970 年代 [[Erwin Neher]] 和 [[Bert Sakmann]] 发明的膜片钳（patch clamp）使研究单个离子通道的电学性质成为可能。两位科学家因此被授予 1991 年诺贝尔生理学或医学奖科学奖。<ref name="Nobel_1991" group="lower-Greek">{{cite press release | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1991/press.html | title = The Nobel Prize in Physiology or Medicine 1991 | publisher = The Royal Swedish Academy of Science | year = 1991 | access-date = 2010-02-21 | url-status = live | archive-url = https://web.archive.org/web/20100324031907/http://nobelprize.org/nobel_prizes/medicine/laureates/1991/press.html | archive-date = 24 March 2010 | df = dmy-all }}</ref> 膜片钳技术证实了离子通道具有分立的电导状态，如打开状态、关闭状态和失活状态。

Several [[neurotoxin]]s, both natural and synthetic, are designed to block the action potential. [[Tetrodotoxin]] from the [[pufferfish]] and [[saxitoxin]] from the ''[[Gonyaulax]]'' （the [[dinoflagellate]] genus responsible for "[[Paralytic shellfish poisoning|red tide]]s"） block action potentials by inhibiting the voltage-sensitive sodium channel;<ref name="TTX_refs" group="lower-alpha">{{cite journal | vauthors = Milligan JV, Edwards C | title = Some factors affecting the time course of the recovery of contracture ability following a potassium contracture in frog striated muscle | journal = The Journal of General Physiology | volume = 48 | issue = 6 | pages = 975–83 | date = July 1965 | pmid = 5855511 | pmc = 2195447 | doi = 10.1085/jgp.48.6.975 }}<br />* {{cite book | vauthors = Ritchie JM, Rogart RB | title = Reviews of Physiology, Biochemistry and Pharmacology, Volume 79 | chapter = The binding of saxitoxin and tetrodotoxin to excitable tissue | volume = 79 | pages = 1–50 | year = 1977 | pmid = 335473 | doi = 10.1007/BFb0037088 | isbn = 0-387-08326-X | series = Reviews of Physiology, Biochemistry and Pharmacology }}<br />* {{cite journal | vauthors = Keynes RD, Ritchie JM | title = On the binding of labelled saxitoxin to the squid giant axon | journal = Proceedings of the Royal Society of London. Series B, Biological Sciences | volume = 222 | issue = 1227 | pages = 147–53 | date = August 1984 | pmid = 6148754 | doi = 10.1098/rspb.1984.0055 | bibcode = 1984RSPSB.222..147K | s2cid = 11465181 }}</ref> similarly, [[dendrotoxin]] from the [[mamba|black mamba]] snake inhibits the voltage-sensitive potassium channel. Such inhibitors of ion channels serve an important research purpose, by allowing scientists to "turn off" specific channels at will, thus isolating the other channels' contributions; they can also be useful in purifying ion channels by [[affinity chromatography]] or in assaying their concentration. However, such inhibitors also make effective neurotoxins, and have been considered for use as [[Chemical warfare|chemical weapon]]s. Neurotoxins aimed at the ion channels of insects have been effective [[insecticide]]s; one example is the synthetic [[permethrin]], which prolongs the activation of the sodium channels involved in action potentials. The ion channels of insects are sufficiently different from their human counterparts that there are few side effects in humans.

Several [[neurotoxin]]s, both natural and synthetic, are designed to block the action potential. [[Tetrodotoxin]] from the [[pufferfish]] and [[saxitoxin]] from the ''[[Gonyaulax]]'' （the [[dinoflagellate]] genus responsible for "[[Paralytic shellfish poisoning|red tide]]s"） block action potentials by inhibiting the voltage-sensitive sodium channel;<ref name="TTX_refs" group="lower-alpha">{{cite journal | vauthors = Milligan JV, Edwards C | title = Some factors affecting the time course of the recovery of contracture ability following a potassium contracture in frog striated muscle | journal = The Journal of General Physiology | volume = 48 | issue = 6 | pages = 975–83 | date = July 1965 | pmid = 5855511 | pmc = 2195447 | doi = 10.1085/jgp.48.6.975 }}<br />* {{cite book | vauthors = Ritchie JM, Rogart RB | title = Reviews of Physiology, Biochemistry and Pharmacology, Volume 79 | chapter = The binding of saxitoxin and tetrodotoxin to excitable tissue | volume = 79 | pages = 1–50 | year = 1977 | pmid = 335473 | doi = 10.1007/BFb0037088 | isbn = 0-387-08326-X | series = Reviews of Physiology, Biochemistry and Pharmacology }}<br />* {{cite journal | vauthors = Keynes RD, Ritchie JM | title = On the binding of labelled saxitoxin to the squid giant axon | journal = Proceedings of the Royal Society of London. Series B, Biological Sciences | volume = 222 | issue = 1227 | pages = 147–53 | date = August 1984 | pmid = 6148754 | doi = 10.1098/rspb.1984.0055 | bibcode = 1984RSPSB.222..147K | s2cid = 11465181 }}</ref> similarly, [[dendrotoxin]] from the [[mamba|black mamba]] snake inhibits the voltage-sensitive potassium channel. Such inhibitors of ion channels serve an important research purpose, by allowing scientists to "turn off" specific channels at will, thus isolating the other channels' contributions; they can also be useful in purifying ion channels by [[affinity chromatography]] or in assaying their concentration. However, such inhibitors also make effective neurotoxins, and have been considered for use as [[Chemical warfare|chemical weapon]]s. Neurotoxins aimed at the ion channels of insects have been effective [[insecticide]]s; one example is the synthetic [[permethrin]], which prolongs the activation of the sodium channels involved in action potentials. The ion channels of insects are sufficiently different from their human counterparts that there are few side effects in humans.

==History历史==

==动作电位研究的历史==

[[Image:PurkinjeCell.jpg|thumb|left|Image of two [[Purkinje cell]]s （labeled as '''A'''） drawn by [[Santiago Ramón y Cajal]] in 1899. Large trees of [[dendrite]]s feed into the [[soma (biology)|soma]], from which a single [[axon]] emerges and moves generally downwards with a few branch points. The smaller cells labeled '''B''' are [[granule cell]]s.

[[Image:PurkinjeCell.jpg|thumb|left|Image of two [[Purkinje cell]]s （labeled as '''A'''） drawn by [[Santiago Ramón y Cajal]] in 1899. Large trees of [[dendrite]]s feed into the [[soma (biology)|soma]], from which a single [[axon]] emerges and moves generally downwards with a few branch points. The smaller cells labeled '''B''' are [[granule cell]]s.

两个浦肯野细胞的图像（标记为'''A'''），由圣地亚哥·拉蒙·卡哈尔于1899年绘制。大树状树状的树状物进入索玛，从中出现单个轴突，并通常向下移动，并带有几个分支点。标记B的较小细胞  是颗粒细胞s。|alt=Hand drawn figure of two Purkinje cells side by side with dendrites projecting upwards that look like tree branches and a few axons projected downwards that connect to a few granule cells at the bottom of the drawing.]]

两个浦肯野细胞的图像（标记为'''A'''），由圣地亚哥·拉蒙·卡哈尔于1899年绘制。大树状树状的树状物进入索玛，从中出现单个轴突，并通常向下移动，并带有几个分支点。标记B的较小细胞  是颗粒细胞s。|alt=Hand drawn figure of two Purkinje cells side by side with dendrites projecting upwards that look like tree branches and a few axons projected downwards that connect to a few granule cells at the bottom of the drawing.]]

The role of electricity in the nervous systems of animals was first observed in dissected [[frog]]s by [[Luigi Galvani]], who studied it from 1791 to 1797.<ref name="piccolino_1997" group="lower-alpha">{{cite journal | vauthors = Piccolino M | title = Luigi Galvani and animal electricity: two centuries after the foundation of electrophysiology | journal = Trends in Neurosciences | volume = 20 | issue = 10 | pages = 443–8 | date = October 1997 | pmid = 9347609 | doi = 10.1016/S0166-2236(97)01101-6 | s2cid = 23394494 }}</ref> Galvani's results stimulated [[Alessandro Volta]] to develop the [[Voltaic pile]]—the earliest-known [[battery (electricity)|electric battery]]—with which he studied animal electricity （such as [[electric eel]]s） and the physiological responses to applied [[direct current|direct-current]] [[voltage]]s.<ref name="piccolino_2000" group="lower-alpha">{{cite journal | vauthors = Piccolino M | title = The bicentennial of the Voltaic battery (1800-2000): the artificial electric organ | journal = Trends in Neurosciences | volume = 23 | issue = 4 | pages = 147–51 | date = April 2000 | pmid = 10717671 | doi = 10.1016/S0166-2236(99)01544-1 | s2cid = 393323 }}</ref>

电在动物神经系统中的作用最早是由 Luigi Galvani 在解剖的青蛙中观察到的，他在 1791 年到 1797 年研究了这一现象。Galvani 的研究结果促成Alessandro Volta 发明了伏打电堆（voltaic pile）——已知最早的电池——他用这种电池研究了动物电（如电鳗）以及对直流电压的生理反应。<ref name="piccolino_2000" group="lower-alpha">{{cite journal | vauthors = Piccolino M | title = The bicentennial of the Voltaic battery (1800-2000): the artificial electric organ | journal = Trends in Neurosciences | volume = 23 | issue = 4 | pages = 147–51 | date = April 2000 | pmid = 10717671 | doi = 10.1016/S0166-2236(99)01544-1 | s2cid = 393323 }}</ref>

 

电在动物神经系统中的作用最早是由 Luigi Galvani 在解剖的青蛙中观察到的，他从1791年到1797年研究了这一现象。伽伐尼的研究结果激励了Alessandro Volta 发明了伏打电堆（voltaic pile）ーー已知最早的电池ーー他用这种电池研究了动物电（如电鳗）以及对直流电压的生理反应。<ref name="piccolino_2000" group="lower-alpha" />

Scientists of the 19th century studied the propagation of electrical signals in whole [[nerve]]s （i.e., bundles of [[neuron]]s） and demonstrated that nervous tissue was made up of [[cell (biology)|cells]], instead of an interconnected network of tubes （a ''reticulum''）.{{sfnm|1a1=Brazier|1y=1961|2a1=McHenry|2a2=Garrison|2y=1969|3a1=Worden|3a2=Swazey|3a3=Adelman|3y=1975}} [[Carlo Matteucci]] followed up Galvani's studies and demonstrated that [[cell membrane]]s had a voltage across them and could produce [[direct current]]. Matteucci's work inspired the German physiologist, [[Emil du Bois-Reymond]], who discovered the action potential in 1843.<ref name=":21">{{Cite book|title=Emil du Bois-Reymond : neuroscience, self, and society in nineteenth-century Germany|last=Finkelstein | first = Gabriel Ward | name-list-style = vanc |isbn=9781461950325|location=Cambridge, Massachusetts|oclc=864592470|year = 2013}}</ref> The [[conduction velocity]] of action potentials was first measured in 1850 by du Bois-Reymond's friend, [[Hermann von Helmholtz]].<ref name=":22">[[Kathryn Olesko|Olesko, Kathryn M.]], and Frederic L. Holmes. "Experiment, Quantification and Discovery: Helmholtz's Early Physiological Researches, 1843-50". In ''Hermann von Helmholtz and the Foundations of Nineteenth Century Science'', ed. David Cahan, 50-108. Berkeley; Los Angeles; London: University of California, 1994.</ref> To establish that nervous tissue is made up of discrete cells, the Spanish physician [[Santiago Ramón y Cajal]] and his students used a stain developed by [[Camillo Golgi]] to reveal the myriad shapes of neurons, which they rendered painstakingly. For their discoveries, Golgi and Ramón y Cajal were awarded the 1906 [[Nobel Prize in Physiology or Medicine|Nobel Prize in Physiology]].<ref name="Nobel_1906" group="lower-Greek">{{cite press release | url = http://nobelprize.org/medicine/laureates/1906/index.html | title = The Nobel Prize in Physiology or Medicine 1906 | publisher = The Royal Swedish Academy of Science | year = 1906 | access-date = 2010-02-21 | url-status = live | archive-url = https://web.archive.org/web/20081204190959/http://nobelprize.org/medicine/laureates/1906/index.html | archive-date = 4 December 2008 | df = dmy-all }}</ref> Their work resolved a long-standing controversy in the [[neuroanatomy]] of the 19th century; Golgi himself had argued for the network model of the nervous system.

Scientists of the 19th century studied the propagation of electrical signals in whole [[nerve]]s （i.e., bundles of [[neuron]]s） and demonstrated that nervous tissue was made up of [[cell (biology)|cells]], instead of an interconnected network of tubes （a ''reticulum''）.{{sfnm|1a1=Brazier|1y=1961|2a1=McHenry|2a2=Garrison|2y=1969|3a1=Worden|3a2=Swazey|3a3=Adelman|3y=1975}} [[Carlo Matteucci]] followed up Galvani's studies and demonstrated that [[cell membrane]]s had a voltage across them and could produce [[direct current]]. Matteucci's work inspired the German physiologist, [[Emil du Bois-Reymond]], who discovered the action potential in 1843.<ref name=":21">{{Cite book|title=Emil du Bois-Reymond : neuroscience, self, and society in nineteenth-century Germany|last=Finkelstein | first = Gabriel Ward | name-list-style = vanc |isbn=9781461950325|location=Cambridge, Massachusetts|oclc=864592470|year = 2013}}</ref> The [[conduction velocity]] of action potentials was first measured in 1850 by du Bois-Reymond's friend, [[Hermann von Helmholtz]].<ref name=":22">[[Kathryn Olesko|Olesko, Kathryn M.]], and Frederic L. Holmes. "Experiment, Quantification and Discovery: Helmholtz's Early Physiological Researches, 1843-50". In ''Hermann von Helmholtz and the Foundations of Nineteenth Century Science'', ed. David Cahan, 50-108. Berkeley; Los Angeles; London: University of California, 1994.</ref> To establish that nervous tissue is made up of discrete cells, the Spanish physician [[Santiago Ramón y Cajal]] and his students used a stain developed by [[Camillo Golgi]] to reveal the myriad shapes of neurons, which they rendered painstakingly. For their discoveries, Golgi and Ramón y Cajal were awarded the 1906 [[Nobel Prize in Physiology or Medicine|Nobel Prize in Physiology]].<ref name="Nobel_1906" group="lower-Greek">{{cite press release | url = http://nobelprize.org/medicine/laureates/1906/index.html | title = The Nobel Prize in Physiology or Medicine 1906 | publisher = The Royal Swedish Academy of Science | year = 1906 | access-date = 2010-02-21 | url-status = live | archive-url = https://web.archive.org/web/20081204190959/http://nobelprize.org/medicine/laureates/1906/index.html | archive-date = 4 December 2008 | df = dmy-all }}</ref> Their work resolved a long-standing controversy in the [[neuroanatomy]] of the 19th century; Golgi himself had argued for the network model of the nervous system.

==定量模型==

==定量模型==

[[Image:MembraneCircuit.svg|thumb|336px|right|Equivalent electrical circuit for the Hodgkin–Huxley model of the action potential. ''I_m'' and ''V_m'' represent the current through, and the voltage across, a small patch of membrane, respectively. The ''C_m'' represents the capacitance of the membrane patch, whereas the four ''g'''s represent the [[electrical conductance|conductances]] of four types of ions. The two conductances on the left, for potassium （K） and sodium （Na）, are shown with arrows to indicate that they can vary with the applied voltage, corresponding to the [[voltage-gated ion channel|voltage-sensitive ion channels]]. The two conductances on the right help determine the [[resting membrane potential]].

[[Image:MembraneCircuit.svg|thumb|336px|right|动作电位的 Hodgkin–Huxley 模型的等效电路。''I_m'' 和 ''V_m'' 分别表示通过一小块膜的电流和两端的电压。''C_m'' 代表膜片的电容，四个 ''g'' 代表四种离子的电导率。左边的两个电导，钾（K）和钠（Na），带箭头表示其可随施加的电压而变化，对应于电压敏感性离子通道。右侧的两个电导有助于决定静息膜电位。|链接=Special:FilePath/MembraneCircuit.svg]]

 

动作电位的 Hodgkin–Huxley 模型的等效电路。''I_m'' 和 ''V_m'' 分别表示通过一小块膜的电流和两端的电压。''C_m'' 代表膜片的电容，而四个 ''g'' 代表四种离子的电导率。带箭头的左边两个电导，钾（K）和钠（Na），表明它们可以随着施加的电压而变化，对应于电压敏感的离子通道。右侧的两个电导有助于确定静息膜电位。|链接=Special:FilePath/MembraneCircuit.svg]]

 

数学和计算模型对于理解动作电位是必不可少的，通过将模型产生的预测与实验数据进行比对，为理论提供严格的检验。早期神经模型中最重要和最准确的是 Hodgkin-Huxley 模型，它通过一组四个常微分方程（ODEs）来描述动作电位。<ref name="hodgkin_1952" group="lower-alpha" /> 虽然 Hodgkin-Huxley 模型可能是一个带有限制的简化模型，<ref name=":20" group="lower-alpha" /> 但与实际存在的神经膜相比，它的局限性很小 <ref name=":23" />，其复杂性激发了几个更简化的模型，例如 Morris-Lecar 模型[[Morris–Lecar model|l]]<ref name="morris_1981" group="lower-alpha" /> a和 FitzHugh-Nagumo 模型，<ref name="fitzhugh" group="lower-alpha" /> 这两个模型都只有两个耦合的常微分方程。Hodgkin-Huxley 模型和 FitzHugh-Nagumo 模型以及它们的近亲，如 Bonhoeffer-Van der Pol 模型，<ref name="bonhoeffer_vanderPol" group="lower-alpha" /> 已经在数学中得到了很好的研究，<ref name="math_studies" /><ref name=":21" group="lower-alpha" /> 计算，<ref name="computational_studies" /> 和电子学。<ref name="keener_1983" group="lower-alpha" /> 然而，简单的生成电位和动作电位模型并不能准确地再现近阈值神经元刺激速率和刺激形态，特别是对于机械性受体如帕西尼氏小体（Pacinian corpuscle）<ref name=":24" /> 。更多的现代研究侧重于更大、更完整的系统；通过将动作电位模型与神经系统其他部分的模型（如树突和突触）结合起来，研究人员可以研究神经计算和简单反射，如逃逸反射和其他由中枢模式发生器控制的反射。<ref name="cpg" /><ref name="pmid10713861" group="lower-alpha" />

数学和计算模型对于理解动作电位是必不可少的，通过将模型产生的预测与实验数据进行比对，为理论提供严格的检验。早期的神经模型中最重要且最准确的是 Hodgkin-Huxley 模型（Hodgkin–Huxley model），它用四个常微分方程（ODEs）的方程组来描述动作电位。<ref name="hodgkin_1952" group="lower-alpha" /> 与自然中实际的神经膜相比， Hodgkin-Huxley 模型可以说是一个带有限制条件的简化模型 <ref name=":23">{{cite journal | vauthors = Baranauskas G, Martina M | title = Sodium currents activate without a Hodgkin-and-Huxley-type delay in central mammalian neurons | journal = The Journal of Neuroscience | volume = 26 | issue = 2 | pages = 671–84 | date = January 2006 | pmid = 16407565 | pmc = 6674426 | doi = 10.1523/jneurosci.2283-05.2006 }}</ref>，不过其复杂性还启发了几个更为简化的模型，<ref name=":20" group="lower-alpha">*{{cite journal | vauthors = Fitzhugh R | title = Thresholds and plateaus in the Hodgkin-Huxley nerve equations | journal = The Journal of General Physiology | volume = 43 | issue = 5 | pages = 867–96 | date = May 1960 | pmid = 13823315 | pmc = 2195039 | doi = 10.1085/jgp.43.5.867 }}<br />* {{cite journal | vauthors = Kepler TB, Abbott LF, Marder E | title = Reduction of conductance-based neuron models | journal = Biological Cybernetics | volume = 66 | issue = 5 | pages = 381–7 | year = 1992 | pmid = 1562643 | doi = 10.1007/BF00197717 | s2cid = 6789007 }}</ref> 例如 Morris-Lecar 模型[[Morris–Lecar model|l]]<ref name="morris_1981" group="lower-alpha">{{cite journal | vauthors = Morris C, Lecar H | title = Voltage oscillations in the barnacle giant muscle fiber | journal = Biophysical Journal | volume = 35 | issue = 1 | pages = 193–213 | date = July 1981 | pmid = 7260316 | pmc = 1327511 | doi = 10.1016/S0006-3495(81)84782-0 | bibcode = 1981BpJ....35..193M }}</ref> 和 FitzHugh-Nagumo 模型，<ref name="fitzhugh" group="lower-alpha">{{cite journal | vauthors = Fitzhugh R | title = Impulses and Physiological States in Theoretical Models of Nerve Membrane | journal = Biophysical Journal | volume = 1 | issue = 6 | pages = 445–66 | date = July 1961 | pmid = 19431309 | pmc = 1366333 | doi = 10.1016/S0006-3495(61)86902-6 | bibcode = 1961BpJ.....1..445F }}<br />* {{cite journal | vauthors = Nagumo J, Arimoto S, Yoshizawa S | year = 1962 | title = An active pulse transmission line simulating nerve axon | journal = Proceedings of the IRE | volume = 50 | pages = 2061–2070 | doi = 10.1109/JRPROC.1962.288235 | issue = 10 | s2cid = 51648050 }}</ref> 这两个模型都只有两个关联的常微分方程。Hodgkin-Huxley 模型和 FitzHugh-Nagumo 模型及其类似模型，如 Bonhoeffer-Van der Pol 模型，<ref name="bonhoeffer_vanderPol" group="lower-alpha">{{cite journal | vauthors = Bonhoeffer KF | title = Activation of passive iron as a model for the excitation of nerve | journal = The Journal of General Physiology | volume = 32 | issue = 1 | pages = 69–91 | date = September 1948 | pmid = 18885679 | pmc = 2213747 | doi = 10.1085/jgp.32.1.69 }}<br />* {{cite journal | vauthors = Bonhoeffer KF | year = 1953 | title = Modelle der Nervenerregung | journal = Naturwissenschaften | volume = 40 | pages = 301–311 | doi = 10.1007/BF00632438|bibcode = 1953NW.....40..301B | issue = 11 | s2cid = 19149460 }}<br />* {{cite journal | vauthors = Van der Pol B | year = 1926 | title = On relaxation-oscillations | journal = Philosophical Magazine | volume = 2 | pages = 977–992| author-link = Balthasar van der Pol }}<br />* {{cite journal | year = 1928 | title = The heartbeat considered as a relaxation oscillation, and an electrical model of the heart | journal = Philosophical Magazine | volume = 6 | pages = 763–775| vauthors = Van der Pol B, Van der Mark J| author-link1 = Balthasar van der Pol | doi=10.1080/14786441108564652}}<br />* {{cite journal | year = 1929 | title = The heartbeat considered as a relaxation oscillation, and an electrical model of the heart | journal = Arch. Neerl. Physiol. | volume = 14 | pages = 418–443| vauthors = Van der Pol B, van der Mark J| author-link1 = Balthasar van der Pol }}</ref> 已经在数学、<ref name="math_studies">Sato, S; Fukai, H; Nomura, T; Doi, S in {{harvnb|Reeke|Poznanski|Sporns|Rosenberg|2005|loc=''Bifurcation Analysis of the Hodgkin-Huxley Equations'', pp. 459–478.}}<br />* FitzHugh, R in {{harvnb|Schwann|1969|loc=''Mathematical models of axcitation and propagation in nerve'', pp. 12–16.}}<br />* {{harvnb|Guckenheimer|Holmes|1986|pp=12–16}}</ref><ref name=":21" group="lower-alpha">{{cite journal | vauthors = Evans JW | year = 1972 | title = Nerve axon equations. I. Linear approximations | journal = Indiana Univ. Math. J. | volume = 21 | pages = 877–885 | doi = 10.1512/iumj.1972.21.21071 | issue = 9| doi-access = free }}<br />* {{cite journal | vauthors = Evans JW, Feroe J | year = 1977 | title = Local stability theory of the nerve impulse | journal = Math. Biosci. | volume = 37 | pages = 23–50 | doi = 10.1016/0025-5564(77)90076-1 }}</ref> 计算、<ref name="computational_studies">Nelson, ME; Rinzel, J in {{harvnb|Bower|Beeman|1995|loc=''The Hodgkin-Huxley Model'', pp. 29–49.}}<br />* Rinzel, J & Ermentrout, GB; in {{harvnb|Koch|Segev|1989|loc=''Analysis of Neural Excitability and Oscillations'', pp. 135–169.}}</ref> 和电子学 <ref name="keener_1983" group="lower-alpha">{{cite journal | vauthors = Keener JP | year = 1983 | title = Analogue circuitry for the Van der Pol and FitzHugh-Nagumo equations | journal = IEEE Transactions on Systems, Man and Cybernetics | volume = 13 | issue = 5 | pages = 1010–1014 | doi = 10.1109/TSMC.1983.6313098 | s2cid = 20077648 }}</ref> 中有很好的研究。然而，发生器电位（generator potential）和动作电位的简单模型并不能准确地再现近阈值的神经脉冲的频率和波形，尤其是对于帕西尼氏小体（Pacinian corpuscle）<ref name=":24">{{cite journal | vauthors = Biswas A, Manivannan M, Srinivasan MA | title = Vibrotactile sensitivity threshold: nonlinear stochastic mechanotransduction model of the Pacinian Corpuscle | journal = IEEE Transactions on Haptics | volume = 8 | issue = 1 | pages = 102–13 | year = 2015 | pmid = 25398183 | doi = 10.1109/TOH.2014.2369422 | s2cid = 15326972 | url = https://zenodo.org/record/894772 }}</ref> 之类的机械感觉受体。更现代的研究侧重于更大的、更为整合的系统；通过将动作电位模型与神经系统其他部分（如树突和突触）的模型结合起来，研究人员可以研究神经计算和简单反射，如逃逸反射和其他由中枢模式发生器控制的反射。<ref name="cpg">Getting, PA in {{harvnb|Koch|Segev|1989|loc=''Reconstruction of Small Neural Networks'', pp. 171–194.}}</ref><ref name="pmid10713861" group="lower-alpha">{{cite journal | vauthors = Hooper SL | title = Central pattern generators | journal = Current Biology | volume = 10 | issue = 5 | pages = R176–R179 | date = March 2000 | pmid = 10713861 | doi = 10.1016/S0960-9822(00)00367-5 | citeseerx = 10.1.1.133.3378 | s2cid = 11388348 }}</ref>

==References==

==References==