Zhabotinsky A M
Department of Chemistry and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Biophys J. 2000 Nov;79(5):2211-21. doi: 10.1016/S0006-3495(00)76469-1.
A mathematical model is presented of autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII) and its dephosphorylation by a phosphatase. If the total concentration of CaMKII subunits is significantly higher than the phosphatase Michaelis constant, two stable steady states of the CaMKII autophosphorylation can exist in a Ca(2+) concentration range from below the resting value of the intracellular [Ca(2+)] to the threshold concentration for induction of long-term potentiation (LTP). Bistability is a robust phenomenon, it occurs over a wide range of parameters of the model. Ca(2+) transients that switch CaMKII from the low-phosphorylated state to the high-phosphorylated one are in the same range of amplitudes and frequencies as the Ca(2+) transients that induce LTP. These results show that the CaMKII-phosphatase bistability may play an important role in long-term synaptic modifications. They also suggest a plausible explanation for the very high concentrations of CaMKII found in postsynaptic densities of cerebral neurons.
本文提出了一种关于Ca(2+)/钙调蛋白依赖性蛋白激酶（CaMKII）自磷酸化及其被磷酸酶去磷酸化的数学模型。如果CaMKII亚基的总浓度显著高于磷酸酶的米氏常数，那么在细胞内[Ca(2+)]的静息值以下至诱导长时程增强（LTP）的阈值浓度的Ca(2+)浓度范围内，CaMKII自磷酸化可存在两种稳定的稳态。双稳态是一种稳健的现象，它在模型的广泛参数范围内都会出现。将CaMKII从低磷酸化状态转换为高磷酸化状态的Ca(2+)瞬变，其幅度和频率范围与诱导LTP的Ca(2+)瞬变相同。这些结果表明，CaMKII-磷酸酶双稳态可能在长期突触修饰中起重要作用。它们还为在脑神经元突触后致密物中发现的非常高浓度的CaMKII提供了一个合理的解释。
