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第五章 肌细胞的收缩 肌肉的分类及肌细胞之间的联系特征: 骨骼肌 : 细胞之间没有紧密连接,互不联系 心肌 : 细胞之间有闰盘连接,为机能合胞体 单一单位平滑肌 :类似平滑肌 多单位平滑肌 :类似骨骼肌 肌肉收缩与人体功能

第五章 肌细胞的收缩 肌肉的分类及肌细胞之间的联系特征: 骨骼肌 : 细胞之间没有紧密连接,互不联系 心肌 : 细胞之间有闰盘连接,为机能合胞体 单一单位平滑肌 :类似平滑肌 多单位平滑肌 :类似骨骼肌 肌肉收缩与人体功能. 横纹肌. 平滑肌.

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第五章 肌细胞的收缩 肌肉的分类及肌细胞之间的联系特征: 骨骼肌 : 细胞之间没有紧密连接,互不联系 心肌 : 细胞之间有闰盘连接,为机能合胞体 单一单位平滑肌 :类似平滑肌 多单位平滑肌 :类似骨骼肌 肌肉收缩与人体功能

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  1. 第五章 肌细胞的收缩 • 肌肉的分类及肌细胞之间的联系特征: 骨骼肌:细胞之间没有紧密连接,互不联系 心肌:细胞之间有闰盘连接,为机能合胞体 单一单位平滑肌:类似平滑肌 多单位平滑肌:类似骨骼肌 • 肌肉收缩与人体功能 横纹肌 平滑肌

  2. Albert von Szent-Györgyi Nagyrapolt(A.森特–焦尔季,匈牙利人)发现肌肉收缩原理,获1937年诺贝尔生理学与医学奖("for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid“) • 骨骼肌占体重的40% • 肌肉的病种很多,研究肌肉很有临床意义

  3. 第一节 神经-骨骼肌接头处的兴奋传递 • 骨骼肌受运动神经支配,肌肉本身没有自律性; • 运动神经末梢释放乙酰胆碱(acetylcholine, Ach); • 乙酰胆碱的量子式释放(quantal release); • 神经-骨骼肌接头(简称神经-肌接头)的结构; • 运动神经APAch释放骨骼肌细胞AP

  4. 一、神经-肌接头处的兴奋传递是化学传递

  5. SIR BERNARD KATZ (Great Britain) Ulf von Euler (Sweden) Julius Axelrod (USA) 1970 Nobel Laureate in Physiology or Medicine "for their discoveries concerning the humoral transmittors in the nerve terminals and the mechanism for their storage, release and inactivation"

  6. Sir Bernard Katz’s Work His research uncovered fundamental properties of synapses, the junctions across which nerve cells signal to each other and to other types of cells. By the 1950s, he was studying the biochemistry and action of acetylcholine, a signalling molecule with which synapses linking "motor nerves" to muscles stimulate contraction. Katz won the Nobel for his discovery that neurotransmitter release at synapses is "quantal"--that is, that at any particular synapse the amount of neurotransmitter released is never less than a certain amount, and if more is always an integral number times this amount. This circumstance arises, scientists now know, because, prior to their release into the synaptic gap, transmitter molecules reside in like-sized subcellular packages known as synaptic vesicles (more at exocytosis).

  7. Julius Axelrod’sWork Axelrod received his Nobel Prize for his work on the release, reuptake and storage of the neurotransmittersepinephrine and norepinephrine, also known as adrenaline and noradrenaline. Working on monoamine oxidase (MAO) inhibitors in 1957, Axelrod showed that catecholamine neurotransmitters do not merely stop working after they are released into the synapse. Instead, neurotransmitters are recaptured (reuptaken) by the pre-synaptic nerve ending, and recycled for later transmissions. He theorized that epinephrine is held in tissues in an inactive form and is liberated by the nervous system when needed. This research laid the groundwork for later selective serotonin reuptake inhibitors (SSRIs), such as Prozac, which block the reuptake of another neurotransmitter, serotonin.

  8. 我系著名生理学家张锡钧院士----发明乙酰胆碱定量测定法我系著名生理学家张锡钧院士----发明乙酰胆碱定量测定法

  9. Henry Hallett Dale (Great Britain) Otto Loewi (Germany) 1936 Nobel Laureate in Physiology or Medicine "for their discoveries relating to chemical transmission of nerve impulses"

  10. Dale’s contribution During the 1940s Dale was embroiled in the scientific debate over the nature of signaling at the synapse. Dale and others believed that signaling at the synapse was chemical, while John Carew Eccles and others believed that the synapse was electrical. It was later found that most synaptic signalling is chemical, but there are some synapses that are electrical. Dale also originated the scheme used to differentiate neurons according to what neurotransmitter they release. Thus, neurons releasing norepinephrine (a.k.a. noradrenaline) are called noradrenergic, neurons releasing GABA are GABAergic, and so on. This scheme is related to Dale's principle (sometimes erroneously referred to as Dale's Law). This principle states that each neuron releases only one type of neurotransmitter. Dale's principle has been shown to be false; many neurons release neuropeptides in addition to amino acids or amines (Bear, et al. 2001).

  11. 运动神经末梢释放Ach如何引起肌细胞的电变化?运动神经末梢释放Ach如何引起肌细胞的电变化? Ach  运动终板的N2型ACH受体  Na+、K+、少量Ca2+通道开放  终板电位(endplate potential) (去极化型局部电位)  终板附近肌细胞膜动作电位

  12. 一、神经末稍的Ach量子式释放(quantal release) • (Kats) • 以Ach囊泡为单位(含10000个Ach分子) • Ach引起终板电位和微终板电位 终板电位(endplate potential, EPP): 运动神经传出冲动,末稍Ach释放引起的终板膜去极化型局部电位,幅度可达50mV,超过肌细胞膜动作电位阈值的3-4倍,可保证神经肌肉接头1:1的传递关系。 微终板电位(miniature endplate potential, MEPP):个别Ach囊泡自发释放所致的微小电变化(去极化型局部电位,频率约每秒1次,幅度约为0.4mV,由一个Ach囊泡释放引起)。

  13. 终板电位的测量

  14. 二、神经末稍释放Ach囊泡需神经末稍内的Ca2+触发二、神经末稍释放Ach囊泡需神经末稍内的Ca2+触发 • 以Ach囊泡为单位(含10000个Ach分子) • Ach引起终板电位和微终板电位 终板电位(endplate potential, EPP): 运动神经传出冲动,末稍Ach释放引起的终板膜去极化型局部电位,幅度可达50 mV,超过肌细胞膜动作电位阈值的3-4倍,可保证神经肌肉接头1:1的传递关系。 微终板电位(miniature endplate potential, MEPP):个别Ach囊泡自发释放所致的微小电变化(去极化型局部电位,频率约每秒1次,幅度约为0.4mV,由一个Ach囊泡释放引起)。

  15. 三、终板电位是由于Ach受体阳离子通道开放而产生的三、终板电位是由于Ach受体阳离子通道开放而产生的 • Ach受体阳离子通道是一种配体门控离子通道

  16. Ach的清除和神经-肌接头传递的干扰 • 胆碱酯酶: 及时(0.2 sec)清除释放的Ach • 美洲箭毒和银环蛇毒素可同Ach竞争性地与终板 膜Ach受体牢固结合,阻断神经肌接头传递。 • 有机磷农药和新斯的明抑制胆碱酯酶

  17. 第二节 横纹肌的收缩与舒张 一、横纹肌细胞的肌原纤维和肌管系统 (一) 肌节(sarcomere,原名肌小节): 是肌细胞舒缩的基本单位,其长度变动范围1.5-3.5m, 安静时2.0-2.2m。 1. 肌原纤维(myofibril)  1-2m, 纵贯肌纤维全 长,一个肌细胞有多达上千条肌原纤维,有明暗 交替的明带和暗带;由粗肌丝和细肌丝组成。暗带的长度比较固定(1.5 m)。明带的长短随肌细胞的伸缩而变化。

  18. M线 明带 暗带 肌小节 Z线 Z线 Z线

  19. 肌丝:粗肌丝,细肌丝 M线:把粗肌丝捆绑在一起 Z线:把细肌丝捆绑在一起

  20. 暗带 明带 明带 Z线 Z线 H带

  21. 2. 肌管系统 • 横管系统(T管):肌细胞内陷形成,在Z线附近环绕肌原纤维。与细胞外液相通,但不与肌浆相通,也不与纵管相通,是肌细胞膜动作电位传入肌细胞深部的膜系统。 • 纵管系统(L管,肌浆网):是另一套管道系统,不与细胞外液或肌浆沟通,也不与横管相通,在近横管处膨大为终末池,是钙池。

  22. 肌质网的结构及贮Ca2+机制 • 纵行肌质网(LSR):包绕在肌原纤维周围,有钙 泵。 • 连接肌质网(junctional SR)或终池(terminal cisterna):有大量Ca2+结合蛋白,其中主要是钙扣押素(calsequestrin);同时有钙释放通道(ryanodine受体)。

  23. 三联管(triad)结构: 紧靠横管两侧有终末池围绕形成,膜之间有12nm间隙。是肌细胞膜动作电位信号传向肌浆网的结构基础。

  24. 二、骨骼肌细胞的兴奋收缩耦联 • (excitation-contraction coupling) • 指由肌细胞膜动作电位转化为肌细胞收缩的过程。 • 兴奋收缩耦联过程: 1. 肌细胞膜AP沿横管传向肌细胞深部; 2. 横管AP引发终末池Ca2+通道开放,Ca2+释放; 3. 肌浆Ca2+浓度升高诱发肌丝滑行,肌细胞缩短。

  25. 横管动作电位如何引发终末池的Ca2+释放? 1)骨骼肌:见后图。 2)心肌: Ca2+诱导的Ca2+释放。 • 释放入肌浆的Ca2+的清除:肌浆网钙泵

  26. · · · · · · · · · · · Ca2+ · · · · · · · · · Ca2+ · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 横管动作电位引发终末池的Ca2+释放机制示意图 静息时 兴奋时 终末池 横管

  27. 骨骼肌收缩的分子机制:肌丝滑行学说 • 50年代初期Huxley提出滑行学说(sliding theory): 肌细胞收缩时并不是肌丝本身的缩短,而是肌小节 内粗细肌丝之间的滑行。 • 滑行学说的证据: 1. 肌肉收缩时暗带长度不变,明带长度缩短; 2. 暗带中央H带变窄,说明肌肉收缩时细肌丝也没 有缩短,只是向暗带中央移动,与粗肌丝发生更 大重叠。

  28. 暗带 明带 明带 Z线 Z线 H带

  29. 粗肌丝:肌凝蛋白(肌球蛋白,myosin) • 肌丝肌纤蛋白(肌动蛋白,actin) 细肌丝:原肌凝蛋白 (tropomyosin) 肌钙蛋白 (troponin) • 原肌凝蛋白:在肌肉静息时阻挡肌凝蛋白与肌纤蛋 白相互作用。 • 肌钙蛋白:为Ca2+受体,有三个亚基。与Ca2+结合 后,可使原肌凝蛋白去阻抑。 收缩蛋白 调节蛋白

  30. 肌丝滑行过程: 肌细胞膜动作电位沿横管传入三联管处  肌浆网终末池释放Ca2+  Ca2+与肌钙蛋白结合  原肌凝蛋白变构,去阻抑  肌凝蛋白头部(横桥)与肌纤蛋白结合  横桥消耗ATP摆动,细肌丝向M线方向滑行,肌小节缩短

  31. 三、肌浆网Ca2+释放和重摄取的调控 • (一)Ryanodine受体与Ca2+释放 • Ryanodine受体:Ca2+释放通道,被L型钙通道的激活所激活 • 心肌收缩对细胞外Ca2+内流依赖性强;通过L型钙通道的构 象变化机制激活SR引起Ca2+的大量释放。 • 骨骼肌收缩对细胞外Ca2+内流依赖性弱;通过L型钙通道的钙 诱导钙释放机制(Ca2+-induced Ca2+ release)激活SR引起 Ca2+大量释放。

  32. 骨骼肌 心肌

  33. (二)肌肉舒张时胞浆Ca2+浓度的下降机制 骨骼肌(Ca2+无进出): 1. SR上的钙泵:2 Ca2+/ATP (100%) 2. 肌钙蛋白:暂时可使肌浆钙浓度下降。 心肌(有Ca2+内流): 1. SR上的钙泵重摄取(70%) 2. 肌膜钙泵驱出细胞(2%) 3. Na+-Ca2+交换体(28%)

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