Montes de Oca Balderas Pavel, Montes de Oca Balderas Horacio
Unit of Dynamic Neurobiology, Neurochemistry Deprtment Instituto Nacional de Neurología y Neurocirugía, Insurgentes Sur #3877, Col. La Fama, C.P. 14269 Ciudad de México, Mexico.
BMC Biophys. 2018 Feb 12;11:3. doi: 10.1186/s13628-018-0043-3. eCollection 2018.
Astrocytes were conceived for decades only as supporting cells of the brain. However, the observation of Ca2+ waves in astrocyte synctitia, their neurotransmitter receptor expression and gliotransmitter secretion suggested a role in information handling, conception that has some controversies. (SN-AmcIP3) is supported by different reports. However, some models contradict this idea and Ca2+ stores are 1000 ± 325 nm apart from the Postsynaptic Density in the Perisynaptic Astrocyte Projections (PAP's), suggesting that SN-AmcIP3 is extrasynaptic. However, this assumption does not consider IP3 Diffusion Coefficient (), that activates IP3 Receptor (IP3R) releasing Ca2+ from intracellular stores.
In this work we idealized a model of a PAP (PAPm) to perform an order of magnitude analysis of IP3 diffusion using a transient mass diffusion model. This model shows that IP3 forms a concentration gradient along the PAPm that reaches the steady state in milliseconds, three orders of magnitude before IP3 degradation. The model predicts that IP3 concentration near the Ca2+ stores may activate IP3R, depending upon Phospholipase C (PLC) number and activity. Moreover, the PAPm supports that IP3 and extracellular Ca2+ entry synergize to promote global Ca2+ transients.
The model presented here indicates that Ca2+ stores position in PAP's does not limit SN-AmcIP3.
几十年来,星形胶质细胞一直被认为只是大脑的支持细胞。然而,在星形胶质细胞合体中观察到的钙离子波、它们的神经递质受体表达以及神经胶质递质分泌表明其在信息处理中发挥作用,这一观点存在一些争议。不同的报告支持(SN - AmcIP3)。然而,一些模型与这一观点相矛盾,并且在突触周围星形胶质细胞突起(PAP)中,钙离子储存与突触后致密物相距1000±325纳米,这表明SN - AmcIP3位于突触外。然而,这一假设没有考虑激活IP3受体(IP3R)从细胞内储存释放钙离子的IP3扩散系数()。
在这项工作中,我们构建了一个PAP模型(PAPm),使用瞬态质量扩散模型对IP3扩散进行量级分析。该模型表明,IP3沿PAPm形成浓度梯度,在数毫秒内达到稳态,这比IP3降解提前三个数量级。该模型预测,钙离子储存附近的IP3浓度可能会激活IP3R,这取决于磷脂酶C(PLC)的数量和活性。此外,PAPm支持IP3和细胞外钙离子内流协同促进全局钙离子瞬变。
这里提出的模型表明,PAP中钙离子储存的位置并不限制SN - AmcIP3。