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: 7333679
• 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/7333679
• 关键词: Physical; chemical; Aspects; Cell; Tissue

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 initiated 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 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. 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 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.

细胞和组织的兴奋性是一种基本的生理功能，它使生物体能够感知环境并对其作出反应。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。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一些反常现象。这些变化包括神经轴突的表面原生质层的可逆体积、温度和光学变化，这些变化与动作电位波形的到达一致。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，这种相变是由钙等二价阳离子与钠、钾等一价阳离子交换引起的。我们之前对灌注轴突的实验清楚地表明，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“全部或没有”的方式兴奋。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诱导生物分子组装的这些变化，我们正在研究在接近生理溶液条件下合成“仿生”阴离子聚合物凝胶的这些过程。研究这些凝胶模型系统的一个优点是，它们的结构、组成和成分之间的相互作用可以被仔细控制，这与在活组织中不同。特别是，在合成聚丙烯酸酯凝胶中，Ferenc Horkay观察到，即使离子结合很弱且完全可逆，周围液体中二价阳离子浓度的微小变化也会引起凝胶中链刚度的显著变化。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载荷，为在广泛的长度尺度上研究这些生物学相关现象提供了补充信息。这些基础研究使我们对神经兴奋的物理机制有了更深入的了解。