Shuvaev Andrey, Belozor Olga, Shuvaev Anton
Institute of Fundamental Biology and Biotechnology, Siberian Federal University, 660041 Krasnoyarsk, Russia.
Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia.
Biology (Basel). 2024 Jul 26;13(8):566. doi: 10.3390/biology13080566.
In our study, we simulate the release of glutamate, a neurotransmitter, from the presynaptic cell by modeling the diffusion of glutamate into both synaptic and extrasynaptic space around the synapse. We have also incorporated a new factor into our model: convection. This factor represents the process by which the body clears glutamate from the synapse. Due to this process, the physiological mechanisms that typically prevent glutamate from spreading beyond the synapse are altered. This results in a different distribution of glutamate concentrations, with higher levels outside the synapse than inside it. The variety of biological effects that occur in response to this extrasynaptic glutamate highlights the importance of preventing neurotransmitters from spreading beyond the synapse. We aim to explain the physical reasons behind these biological effects, which are observed as excitotoxicity. Our results show that preventing the spread of glutamate outside the synapse increases the amount of information exchanged within the synapse and its surroundings for frequencies of glutamate release up to 30-50 Hz, followed by a decrease. Additionally, we find that the rate at which glutamate is cleared from the synapse is effective at relatively low levels (≤0.5 nm/μs in our calculation grid) and remains constant at higher levels.
在我们的研究中，我们通过对谷氨酸在突触周围的突触间隙和突触外空间扩散进行建模，来模拟突触前细胞释放神经递质谷氨酸的过程。我们还在模型中纳入了一个新因素：对流。该因素代表身体从突触清除谷氨酸的过程。由于这个过程，通常防止谷氨酸扩散到突触之外的生理机制发生了改变。这导致谷氨酸浓度分布不同，突触外的浓度高于突触内。对这种突触外谷氨酸产生的各种生物学效应凸显了防止神经递质扩散到突触之外的重要性。我们旨在解释这些作为兴奋性毒性观察到的生物学效应背后的物理原因。我们的结果表明，对于高达30 - 50赫兹的谷氨酸释放频率，防止谷氨酸在突触外扩散会增加突触及其周围交换的信息量，随后信息量会减少。此外，我们发现谷氨酸从突触清除的速率在相对较低水平（在我们的计算网格中≤0.5纳米/微秒）时有效，在较高水平时保持恒定。
