Physical-chemical Aspects Of Cell And Tissue Excitabilit

细胞和组织兴奋性的物理化学方面

• 批准号: 6991175
• 负责人: ICHIJI TASAKI
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6991175
• 关键词: action potentials; anions; axon; biomimetics; biophysics; divalent cations; electric field; gel; molecular assembly /self assembly; neural conduction; neurons; physical chemical interaction; polyacrylate

Excitability of cells and tissues is an essential physiological function that allows organisms to sense their environment and respond to it. The primary goal of this work is to explain key physical-chemical features of cell and tissue excitability, many aspects of which are still poorly understood. Widely accepted theories of nerve excitability do not explain several anomalous phenomena that we have shown are necessary for excitation to occur. These include reversible volume, temperature, and optical changes of the superficial protoplasmic layer of nerve axons, which coincide with the arrival of the action potential waveform. We have obtained further evidence that these physical changes accompany a phase transition that occurs in nerve cells, fibers, and synapses caused by the exchange of divalent cations like calcium with monovalent cations like sodium and potassium. Our previous experiments with perfused axons clearly implicate divalent/monovalent cation exchange as a mechanism by which nerve fibers can be excited in an "all or none" manner. To understand the physical chemical basis of these temperature and volumetric changes, particularly how divalent/monovalent cation exchange can induce such changes in biomolecular assemblies, we are studying these processes in synthetic "biomimetic" anionic polymer gels under nearly physiological 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. We are also investigating biophysical aspects of stimulation by electromagnetic induction (magnetic stimulation) in the central and peripheral nervous systems. Pedro Miranda has performed detailed calculations using a finite element method (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.

细胞和组织的兴奋性是一种重要的生理功能，使生物体能够感知其环境并对其做出反应。这项工作的主要目标是解释细胞和组织兴奋性的关键物理化学特征，其中许多方面仍然知之甚少。被广泛接受的神经兴奋性理论并不能解释我们已经证明的兴奋发生所必需的几种异常现象。这些包括可逆的体积，温度和神经轴突的表面原生质层的光学变化，这与动作电位波形的到来相一致。我们已经获得了进一步的证据，这些物理变化伴随着发生在神经细胞，纤维和突触中的相变，这是由二价阳离子（如钙）与一价阳离子（如钠和钾）的交换引起的。我们先前的灌注轴突实验清楚地表明，二价/单价阳离子交换是一种机制，通过这种机制，神经纤维可以以“全或无”的方式被激发。为了了解这些温度和体积变化的物理化学基础，特别是二价/单价阳离子交换如何在生物分子组装中诱导这种变化，我们正在研究这些过程中合成的“仿生”阴离子聚合物凝胶在接近生理条件下。研究这些凝胶模型系统的行为的一个优点是，它们的结构、组成和它们的组分之间的相互作用可以被仔细控制，这与活组织不同。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引起凝胶中链刚度的显著变化，即使离子结合是弱的并且完全可逆。各种物理化学和聚合物物理为基础的技术，包括中子，X射线和光散射，以及渗透溶胀，和机械负荷提供了补充信息，研究这些生物学相关的现象在很宽的范围内的长度尺度。这些基础研究正在导致对神经兴奋背后的物理机制的更深入理解。 我们还在研究中枢和外周神经系统中电磁感应（磁刺激）刺激的生物物理学方面。佩德罗·米兰达（Pedro Miranda）使用有限元法（FEM）进行了详细计算，以预测磁刺激期间大脑中感应的电场和电流密度分布。以前，我们发现，组织的异质性和各向异性的电导率有助于显着扭曲的诱导场，甚至在某些地区创建兴奋性或抑制性的“热点”。这些现象可能在解释或推断兴奋区域或部位以及确定神经兴奋来源方面具有重要的临床后果。最近，我们集中在可能的物理机制皮层兴奋。