Bartlett Paula J, Cloete Ielyaas, Sneyd James, Thomas Andrew P
Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
Department of Mathematics, The University of Auckland, Auckland, New Zealand.
iScience. 2020 May 22;23(5):101062. doi: 10.1016/j.isci.2020.101062. Epub 2020 Apr 13.
Ca oscillations that depend on inositol-1,4,5-trisphosphate (IP) have been ascribed to biphasic Ca regulation of the IP receptor (IPR) or feedback mechanisms controlling IP levels in different cell types. IP uncaging in hepatocytes elicits Ca transients that are often localized at the subcellular level and increase in magnitude with stimulus strength. However, this does not reproduce the broad baseline-separated global Ca oscillations elicited by vasopressin. Addition of hormone to cells activated by IP uncaging initiates a qualitative transition from high-frequency spatially disorganized Ca transients, to low-frequency, oscillatory Ca waves that propagate throughout the cell. A mathematical model with dual coupled oscillators that integrates Ca-induced Ca release at the IPR and mutual feedback mechanisms of cross-coupling between Ca and IP reproduces this behavior. Thus, multiple Ca oscillation modes can coexist in the same cell, and hormonal stimulation can switch from the simpler to the more complex to yield robust signaling.
依赖于肌醇-1,4,5-三磷酸（IP）的钙振荡已归因于IP受体（IPR）的双相钙调节或控制不同细胞类型中IP水平的反馈机制。在肝细胞中进行IP光解会引发钙瞬变，这些瞬变通常定位于亚细胞水平，并随着刺激强度的增加而增大。然而，这并不能重现由血管加压素引发的广泛的基线分离的全局钙振荡。向通过IP光解激活的细胞中添加激素会引发从高频空间无序钙瞬变到低频振荡钙波的定性转变，这种钙波会在整个细胞中传播。一个具有双耦合振荡器的数学模型整合了IPR处钙诱导的钙释放以及钙与IP之间交叉耦合的相互反馈机制，再现了这种行为。因此，多种钙振荡模式可以在同一细胞中共存，并且激素刺激可以从较简单的模式切换到更复杂的模式以产生强大的信号传导。
