在神经肌肉细胞培养中的神经递质释放期间,在突触活性区实验性监测动态
Xiaoping Sun1, Bruce Yazejian1, Arthur Peskoff1
1Department of Physiology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
The European journal of neuroscience
|March 14, 2024
概括
在Xenopus神经肌细胞中的依赖的 (BK) 通道揭示了活性区动态和神经递质释放. BK通道作为有效的报告员,在活性区域的局部度.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 了解离子 (Ca2+) 在神经终端活性区 (AZ) 中神经递质释放中的精确作用至关重要.
- 已知依赖的 (BK) 通道对细胞内水平敏感,但它们与神经递质释放动态的确切关系尚未完全阐明.
- 靠近电压关闭通道的Ca2+微域的空间和时间动态显著影响细胞反应.
研究的目的:
- 通过实验量化Ca2+进入Xenopus神经肌肉培养中的不同速率和持续时间所导致的瞬间活性区[Ca2+]AZ.
- 为了将这些测量的[Ca2+]AZ水平与神经递质释放相关联.
- 开发和验证一个包含缓冲属性的活区模型,以解释观察到的Ca2+动态.
主要方法:
- 在Xenopus神经肌肉细胞培养物中利用了Ca2+依赖的K (BK) 通道,以测量活性区域Ca2+度 ([Ca2+]AZ).
- 在不同的Ca2+流入条件下,量化了Ca2+尾流和刺激后突触电流 (EPSCs).
- 开发了一个计算活性区 (AZ) 模型,将脂电荷作为高容量,低亲和度缓冲器.
主要成果:
- 峰值[Ca2+]AZ达到~30μM,持续的流入导致~45-60μM,取决于Ca2+的驱动力和流入时间.
- 无论是BK通道电流 (IBK) 还是神经递质释放都依赖于Ca2+微域,这些微域在~0.6 ms的时间常数下崩.
- 与EPSC相比,IBK对[Ca2+]AZ (K1/2~26 μM) 的敏感性更高 (K1/2~36 μM),具有不同的Hill系数 (2.5对于IBK,3.9对于EPSC).
结论:
- 一些BK通道,但很少有Ca2+传感器用于释放,位于Ca2+纳米域内;更大的部分距离更远,可以访问EGTA.
- 神经递质的释放主要取决于达到的[Ca2+]AZ峰值,而不是达到它的时间.
- BK通道是局部[Ca2+]AZ的有价值的记者,与成熟的青神经肌肉结合相比,变异性突触显示出不同的特性.
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