Kinetics, Ca2+ Dependence, and Biophysical Properties of Integrin-Mediated Mechanical Modulation of Transmitter Release from Frog Motor Nerve Terminals
Kinetics, Ca2+ Dependence, and Biophysical Properties of Integrin-Mediated Mechanical Modulation of Transmitter Release from Frog Motor Nerve Terminals
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青蛙运动神经末梢递质释放的整合素介导的机械调节的动力学、Ca2依赖性和生物物理特性
DOI：
10.1523/jneurosci.17-03-00904.1997
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
A. Grinnell
中科院分区：
文献类型：
--
作者：
Bo‐Ming Chen;A. Grinnell
青蛙运动神经末梢的神经递质释放受肌肉长度变化的强烈调制。在生理范围内，每1%的肌肉拉伸，自发和诱发释放增加约10%。由于许多肌纤维在静息长度时不接受阈上突触输入，这种牵张诱导的释放增强构成了脊髓牵张反射的强大外周放大器。通过阻断天然配体的整合素结合的肽抑制释放的拉伸调节。调制随长度线性变化，延迟不超过1-2毫秒，并在新的长度上保持恒定。此外，牵张调制持续在零Ca 2+林格氏，因此，是不依赖于通过牵张激活通道的Ca 2+流入。消除跨膜Ca 2+梯度和缓冲intraterminal Ca 2+到接近正常的静息水平并不能消除调制，这表明它不是Ca 2+从内部存储释放的结果。最后，温度的变化对牵张诱导的终板电位（EPP）振幅或微型EPP（mEPP）频率变化的动力学没有可检测的影响。因此，我们得出结论，拉伸不通过第二信使途径或参与释放途径的分子的化学修饰起作用。相反，存在释放的直接机械调节。我们假设，在突触前膜上的整合素的张力被机械地转换成参与神经递质释放的一个或多个分子的位置或构象的变化，改变对Ca 2+的敏感性或导致囊泡融合的关键反应的平衡。
Neurotransmitter release from frog motor nerve terminals is strongly modulated by change in muscle length. Over the physiological range, there is an ∼10% increase in spontaneous and evoked release per 1% muscle stretch. Because many muscle fibers do not receive suprathreshold synaptic inputs at rest length, this stretch-induced enhancement of release constitutes a strong peripheral amplifier of the spinal stretch reflex. The stretch modulation of release is inhibited by peptides that block integrin binding of natural ligands. The modulation varies linearly with length, with a delay of no more than ∼1-2 msec and is maintained constant at the new length. Moreover, the stretch modulation persists in a zero Ca2+ Ringer and, hence, is not dependent on Ca2+ influx through stretch activated channels. Eliminating transmembrane Ca2+gradients and buffering intraterminal Ca2+ to approximately normal resting levels does not eliminate the modulation, suggesting that it is not the result of release of Ca2+ from internal stores. Finally, changes in temperature have no detectable effect on the kinetics of stretch-induced changes in endplate potential (EPP) amplitude or miniature EPP (mEPP) frequency. We conclude, therefore, that stretch does not act via second messenger pathways or a chemical modification of molecules involved in the release pathway. Instead, there is direct mechanical modulation of release. We postulate that tension on integrins in the presynaptic membrane is transduced mechanically into changes in the position or conformation of one or more molecules involved in neurotransmitter release, altering sensitivity to Ca2+ or the equilibrium for a critical reaction leading to vesicle fusion.
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DOI：
10.1016/s0021-9258(18)37650-6
发表时间：
1988-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Gailit;Erkki I. Ruoslahti
通讯作者：
J. Gailit;Erkki I. Ruoslahti
血小板受体 GPIIb/IIIa 结合特异性的阳离子依赖性变化。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kirchhofer,D;Gailit,J;Ruoslahti,E;Grzesiak,J;Pierschbacher,MD
通讯作者：
Pierschbacher,MD
影响因子：
3.7
作者：
Martin A. Schwartz;Donald E. Ingber;Michael B. Lawrence;T. A. Springer;Claude Lechene;Claude Lechene
通讯作者：
Martin A. Schwartz;Donald E. Ingber;Michael B. Lawrence;T. A. Springer;Claude Lechene;Claude Lechene
影响因子：
--
作者：
RESTREPO, D;BOEKHOFF, I;BREER, H
通讯作者：
BREER, H
DOI：
10.1016/s0021-9258(18)83165-9
发表时间：
1989-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Minta;J. Kao;R. Tsien
通讯作者：
A. Minta;J. Kao;R. Tsien