Department of Mathematics, Bioinformatics and Computer Applications, Maulana Azad National Institute of Technology, Bhopal, 462003, Madhya Pradesh, India.
Cell Biochem Biophys. 2024 Jun;82(2):787-803. doi: 10.1007/s12013-024-01229-5. Epub 2024 Feb 20.
The bioenergetic system of calcium ([Ca]), inositol 1, 4, 5-trisphophate (IP) and nitric oxide (NO) regulate the diverse mechanisms in neurons. The dysregulation in any or all of the calcium, IP and nitric oxide dynamics may cause neurotoxicity and cell death. Few studies are noted in the literature on the interactions of two systems like [Ca] with IP and [Ca] with nitric oxide in neuron cells, which gives limited insights into regulatory and dysregulatory processes in neuron cells. But, no study is available on the cross talk in dynamics of three systems [Ca], IP and NO in neurons. Thus, the cross talk in the system dynamics of [Ca], IP and NO regulation processes in neurons have been studied using mathematical model. The two-way feedback process between [Ca] and IP and two-way feedback process between [Ca] and NO through cyclic guanosine monophosphate (cGMP) with plasmalemmal [Ca]-ATPase (PMCA) have been incorporated in the proposed model. This coupling handles the indirect two-way feedback process between IP and nitric oxide in neuronal cells automatically. The numerical outcomes were acquired by employing the finite element method (FEM) with the Crank-Nicholson scheme (CNS). The present model incorporating the sodium-calcium exchanger (NCX) and voltage-gated calcium channel (VGCC) provides novel insights into the various regulatory and dysregulatory processes due to buffer, IP-receptor, ryanodine receptor, cGMP kinetics through PMCA channel, etc. and their impacts on the interactive spatiotemporal system dynamics of [Ca], IP and NO in neurons. It is concluded that the behavior of different crucial mechanisms is quite different for interactions of two systems of [Ca] and NO and the interactions of three systems of [Ca], IP and nitric oxide in neuronal cell due to mutual regulatory adjustments. The association of several neurological disorders with the alterations in calcium, IP and NO has been explored in neurons.
钙 ([Ca])、肌醇 1,4,5-三磷酸 (IP) 和一氧化氮 (NO) 的生物能量系统调节神经元中的多种机制。任何或所有钙、IP 和一氧化氮动力学的失调都可能导致神经毒性和细胞死亡。文献中很少有关于像 [Ca] 与 IP 和 [Ca] 与神经元细胞中一氧化氮这样的两个系统相互作用的研究,这使得对神经元细胞中调节和失调过程的了解有限。但是,没有关于钙 ([Ca])、IP 和一氧化氮 (NO) 三个系统在神经元中动态相互作用的研究。因此,使用数学模型研究了神经元中 [Ca]、IP 和 NO 调节过程的系统动态相互作用。通过质膜钙-ATP 酶 (PMCA) 中的环鸟苷单磷酸 (cGMP),将 [Ca] 和 IP 之间的双向反馈过程以及 [Ca] 和 NO 之间的双向反馈过程纳入到所提出的模型中。这种耦合自动处理神经元细胞中 IP 和一氧化氮之间的间接双向反馈过程。采用有限元方法 (FEM) 和 Crank-Nicholson 方案 (CNS) 获得数值结果。该模型结合钠钙交换器 (NCX) 和电压门控钙通道 (VGCC),为由于缓冲、IP 受体、ryanodine 受体、通过 PMCA 通道的 cGMP 动力学等引起的各种调节和失调过程提供了新的见解,以及它们对神经元中 [Ca]、IP 和 NO 相互作用的时空系统动态的影响。结论是,由于相互调节调整,两个系统 [Ca] 和 NO 的相互作用以及神经元细胞中三个系统 [Ca]、IP 和一氧化氮的相互作用,不同关键机制的行为是非常不同的。还探讨了几种神经紊乱与钙、IP 和 NO 改变之间的关联。