Physical-chemical Aspects Of Cell And Tissue Excitability

为了了解神经兴奋的物理化学基础，我们正在研究温度和体积变化与神经兴奋性之间的关系。我们正在继续探索二价/一价阳离子交换可以引起这种变化的可能性。为了研究这一假设，我们正在研究生物分子组装中的离子交换，以及在几乎生理溶液条件下合成的仿生阴离子聚合物凝胶中的离子交换。研究这些凝胶模型系统的行为的一个优点是，它们的结构、组成和成分之间的相互作用可以仔细控制，不像在活组织中那样。特别是，在合成聚丙烯酸酯凝胶中，Ferenc Horkay观察到，周围液体中二价阳离子浓度的微小变化可以导致凝胶中链刚性的显著变化，即使离子结合很弱且完全可逆。各种基于物理、化学和聚合物物理的技术，包括中子、X射线和光散射，以及渗透膨胀和机械加载，为在广泛的长度范围内研究这些生物相关现象提供了补充信息。这些基础研究正在加深对神经兴奋背后的物理机制的理解。 在试图了解扩散磁共振信号的生物物理基础的过程中，乌里·内沃成功地构建并测试了一个使用扩散磁共振方法询问器官型培养脑片的实验系统。这项工作已经显示出令人振奋的结果，将测量的扩散系数图的变化与培养组织所受环境条件的变化联系起来。这项工作的一个理论方面是发展模型系统，在模型系统中，我们可以演示微观流动如何在扩散加权磁共振实验中表现为“伪扩散”和信号损失。 在经颅磁刺激(TMS)领域，Pedro Miranda和他的团队与STBB合作，使用有限元方法(FEM)进行了详细的计算，以预测磁刺激期间在大脑中感应的电场和电流密度分布。以前，我们发现组织的异质性和电导率的各向异性都会显著地扭曲感应场，甚至在某些区域产生兴奋或抑制的热点。这些现象在解释或推断兴奋区域或位置以及确定神经兴奋的来源方面都可能产生重大的临床后果。最近，我们集中讨论了大脑皮层兴奋的可能物理机制。一个更长期的目标是将我们的神经组织磁刺激宏观模型与中枢神经系统和三叉神经节神经兴奋性的微观模型结合起来。大脑皮质TMS的更详细的有限元模型正在开发中。

To understand the physical chemical basis of nerve excitation, we are studying the relationships between changes in temperature and volume associated with nerve excitability. We are continuing to explore the possibility that divalent/monovalent cation exchange can induce such changes. To investigate this hypothesis, we are studying ion exchange in biomolecular assemblies, and in synthetic biomimetic anionic polymer gels under nearly physiological solution conditions. An advantage of studying the behavior of these gel model systems is that their structure, composition, and the interactions among their components can be carefully controlled, unlike in living tissue. In particular, in synthetic polyacrylate gels, Ferenc Horkay has observed that minute changes in the concentration of divalent cations in the surrounding liquid can induce significant changes in chain stiffness in the gel, even if ion binding is weak and completely reversible. Various physical chemical and polymer physics-based techniques, including neutron, x-ray and light scattering, as well as osmotic swelling, and mechanical loading provide complementary information with which to study these biologically relevant phenomena over a wide range of length scales. These basic studies are leading to a deeper understanding of the physical mechanisms underlying nerve excitation. In trying to understand the biophysical basis of the diffusion MR signal, Uri Nevo has successfully constructed and tested an experimental system for interrogating organotypic cultured brain slices using diffusion MRI methods. This work has already shown promising results relating changes in the measured diffusion coefficient map to changes in environmental conditions to which the cultured tissue is subjected. A theoretical aspect of this work is the development of model systems in which we can demonstrate how microscopic flows manifest themselves as "pseudo-diffusion" and manifest themselves as signal loss in diffusion weighted MRI experiments. In the area of Transcranial Magnetic Stimulation (TMS), Pedro Miranda and his group, in association with STBB has performed detailed calculations using finite element methods (FEM), to predict the electric field and current density distributions induced in the brain during magnetic stimulation. Previously, we found that both tissue heterogeneity and anisotropy of the electrical conductivity contribute significantly to distort the induced fields, and even to create excitatory or inhibitory hot spots in some regions. These phenomena could have significant clinical consequences both in interpreting or inferring the region or locus of excitation and in determining the source of nerve excitation. More recently, we have focussed on possible physical mechanisms of cortical excitation. A longer term goal is to marry our macroscopic models of magnetic stimulation in nerve tissue with microscopic models of nerve excitability in the CNS and PNS. More detailed FEM models of TMS in the cortex are under development.