Khreesha Lubna, Qaswal Abdallah Barjas, Al Omari Baheth, Albliwi Moath Ahmad, Ababneh Omar, Albanna Ahmad, Abunab'ah Abdelrahman, Iswaid Mohammad, Alarood Salameh, Guzu Hasan, Alshawabkeh Ghadeer, Zayed Fuad Mohammed, Abuhilaleh Mohammad Awad, Al-Jbour Mohammad Nayel, Obeidat Salameh, Suleiman Aiman
School of Medicine, The University of Jordan, Amman 11942, Jordan.
Anesthesia Department, Farah Medical Campus, 18 Mai Zeyadeh Street, Amman 11942, Jordan.
Membranes (Basel). 2021 Nov 1;11(11):851. doi: 10.3390/membranes11110851.
Lithium imposes several cellular effects allegedly through multiple physiological mechanisms. Membrane depolarization is a potential unifying concept of these mechanisms. Multiple inherent imperfections of classical electrophysiology limit its ability to fully explain the depolarizing effect of lithium ions; these include incapacity to explain the high resting permeability of lithium ions, the degree of depolarization with extracellular lithium concentration, depolarization at low therapeutic concentration, or the differences between the two lithium isotopes Li-6 and Li-7 in terms of depolarization. In this study, we implemented a mathematical model that explains the quantum tunneling of lithium ions through the closed gates of voltage-gated sodium channels as a conclusive approach that decodes the depolarizing action of lithium. Additionally, we compared our model to the classical model available and reported the differences. Our results showed that lithium can achieve high quantum membrane conductance at the resting state, which leads to significant depolarization. The quantum model infers that quantum membrane conductance of lithium ions emerges from quantum tunneling of lithium through the closed gates of sodium channels. It also differentiates between the two lithium isotopes (Li-6 and Li-7) in terms of depolarization compared with the previous classical model. Moreover, our study listed many examples of the cellular effects of lithium and membrane depolarization to show similarity and consistency with model predictions. In conclusion, the study suggests that lithium mediates its multiple cellular effects through membrane depolarization, and this can be comprehensively explained by the quantum tunneling model of lithium ions.
锂据称通过多种生理机制产生多种细胞效应。膜去极化是这些机制的一个潜在统一概念。经典电生理学的多个固有缺陷限制了其充分解释锂离子去极化作用的能力；这些缺陷包括无法解释锂离子的高静息通透性、细胞外锂浓度与去极化程度的关系、低治疗浓度下的去极化，或两种锂同位素Li-6和Li-7在去极化方面的差异。在本研究中，我们建立了一个数学模型，该模型将锂离子通过电压门控钠通道的关闭门控进行量子隧穿解释为一种解释锂去极化作用的决定性方法。此外，我们将我们的模型与现有的经典模型进行了比较，并报告了差异。我们的结果表明，锂在静息状态下可实现高量子膜电导，这导致显著的去极化。量子模型推断，锂离子的量子膜电导源于锂通过钠通道的关闭门控进行的量子隧穿。与之前的经典模型相比，它还在去极化方面区分了两种锂同位素（Li-6和Li-7）。此外，我们的研究列举了许多锂的细胞效应和膜去极化的例子，以显示与模型预测的相似性和一致性。总之，该研究表明，锂通过膜去极化介导其多种细胞效应，这可以通过锂离子的量子隧穿模型得到全面解释。
