Keizer J, Levine L
Institute of Theoretical Dynamics, University of California, Davis 95616, USA.
Biophys J. 1996 Dec;71(6):3477-87. doi: 10.1016/S0006-3495(96)79543-7.
A simplified mechanism that mimics "adaptation" of the ryanodine receptor (RyR) has been developed and its significance for Ca2+(-)induced Ca2+ release and Ca2+ oscillations investigated. For parameters that reproduce experimental data for the RyR from cardiac cells, adaptation of the RyR in combination with sarco/endoplasmic reticulum Ca2+ ATPase Ca2+ pumps in the internal stores can give rise to either low [Cai2+] steady states or Ca2+ oscillations coexisting with unphysiologically high [Cai2+] steady states. In this closed-cell-type model rapid, adaptation-dependent Ca2+ oscillations occur only in limited ranges of parameters. In the presence of Ca2+ influx and efflux from outside the cell (open-cell model) Ca2+ oscillations occur for a wide range of physiological parameter values and have a period that is determined by the rate of Ca2+ refilling of the stores. Although the rate of adaptation of the RyR has a role in determining the shape and the period of the Ca2+ spike, it is not essential for their existence. This is in marked contrast with what is observed for the inositol 1,4,5-trisphosphate receptor for which the biphasic activation and inhibition of its activity by Ca2+ are sufficient to produce oscillations. Results for this model are compared with those based on Ca2+(-)induced Ca2+ release alone in the bullfrog sympathetic neuron. This kinetic model should be suitable for analyzing phenomena associated with "Ca2+ sparks," including their merger into Ca2+ waves in cardiac myocytes.
一种模拟兰尼碱受体（RyR）“适应性”的简化机制已被开发出来，并对其在Ca2+诱导的Ca2+释放和Ca2+振荡中的意义进行了研究。对于重现心脏细胞中RyR实验数据的参数，RyR的适应性与内部储存库中的肌浆网/内质网Ca2+ATP酶Ca2+泵相结合，可导致低[Cai2+]稳态或与非生理性高[Cai2+]稳态共存的Ca2+振荡。在这种封闭细胞类型模型中，快速的、依赖适应性的Ca2+振荡仅在有限的参数范围内发生。在存在细胞外Ca2+流入和流出的情况下（开放细胞模型），对于广泛的生理参数值都会出现Ca2+振荡，其周期由储存库中Ca2+的再填充速率决定。尽管RyR的适应速率在决定Ca2+尖峰的形状和周期方面有作用，但对于其存在并非必不可少。这与在肌醇1,4,5-三磷酸受体中观察到的情况形成鲜明对比，对于该受体，Ca2+对其活性的双相激活和抑制足以产生振荡。将该模型的结果与仅基于牛蛙交感神经元中Ca2+诱导的Ca2+释放的结果进行了比较。这种动力学模型应该适用于分析与“Ca2+火花”相关的现象，包括它们在心肌细胞中合并成Ca2+波的现象。
