Friel D D
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106-4975, USA.
Biophys J. 1995 May;68(5):1752-66. doi: 10.1016/S0006-3495(95)80352-8.
[Ca2+]i oscillations have been described in a variety of cells. This study focuses on caffeine-induced [Ca2+]i oscillations in sympathetic neurons. Previous work has shown that these oscillations require Ca2+ entry from the extracellular medium and Ca(2+)-induced Ca2+ release from a caffeine- and ryanodine-sensitive store. The aim of the study was to understand the mechanism responsible for the oscillations. As a starting point, [Ca2+]i relaxations were examined after membrane depolarization and exposure to caffeine. For both stimuli, post-stimulus relaxations could be described by the sum of two decaying exponential functions, consistent with a one-pool system in which Ca2+ transport between compartments is regulated by linear Ca2+ pumps and leaks. After modifying the store to include a [Ca2+]i-sensitive leak, the model also exhibits oscillations such as those observed experimentally. The model was tested by comparing measured and predicted net Ca2+ fluxes during the oscillatory cycle. Three independent fluxes were measured, describing the rates of 1) Ca2+ entry across the plasma membrane, 2) Ca2+ release by the internal store, and 3) Ca2+ extrusion across the plasma membrane and uptake by the internal store. Starting with estimates of the model parameters deduced from post-stimulus relaxations and the rapid upstroke, a set of parameter values was found that provides a good description of [Ca2+]i throughout the oscillatory cycle. With the same parameter values, there was also good agreement between the measured and simulated net fluxes. Thus, a one-pool model with a single [Ca2+]i-sensitive Ca2+ permeability is adequate to account for many of the quantitative properties of steady-state [Ca2+]i oscillations in sympathetic neurons. Inactivation of the intracellular Ca2+ permeability, cooperative nonlinear Ca2+ uptake and extrusion mechanisms, and functional links between plasma membrane Ca2+ transport and the internal store are not required.
细胞内钙离子（[Ca2+]i）振荡已在多种细胞中被描述。本研究聚焦于咖啡因诱导的交感神经元[Ca2+]i振荡。先前的研究表明，这些振荡需要细胞外介质中的钙离子内流以及咖啡因和雷诺丁敏感储存库中的钙诱导钙释放。本研究的目的是了解振荡产生的机制。作为起点，在膜去极化和暴露于咖啡因后检测了[Ca2+]i的松弛情况。对于这两种刺激，刺激后的松弛情况可用两个衰减指数函数之和来描述，这与一个单池系统一致，在该系统中，隔室间的钙离子转运由线性钙离子泵和渗漏调节。在对储存库进行修改以纳入对[Ca2+]i敏感的渗漏后，该模型也表现出如实验中观察到的振荡。通过比较振荡周期中测量的和预测的净钙离子通量对该模型进行了测试。测量了三种独立的通量，分别描述了1）钙离子跨质膜的内流速率、2）内部储存库的钙释放速率以及3）钙离子跨质膜的外排速率和被内部储存库摄取的速率。从根据刺激后松弛情况和快速上升阶段推导的模型参数估计值开始，找到了一组能很好描述整个振荡周期内[Ca2+]i情况的参数值。使用相同的参数值，测量的和模拟的净通量之间也有很好的一致性。因此，具有单个对[Ca2+]i敏感的钙离子通透性的单池模型足以解释交感神经元中稳态[Ca2+]i振荡的许多定量特性。不需要细胞内钙离子通透性的失活、协同非线性钙离子摄取和外排机制以及质膜钙离子转运与内部储存库之间的功能联系。
