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: 6677330
• 负责人: PETER J. BASSER
• 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/6677330
• 关键词: action potentials; animal tissue; biophysics; divalent cations; neural initiation; neural transmission; neurons; synapses

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 fail to explain several anomalous phenomena that we have observed, which we have shown are also necessary for excitation to occur. These include volume and temperature changes of the superficial protoplasmic layer of nerve axons, which coincide with the action potential waveform. We have obtained further evidence that these 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 its components can be carefully controlled, unlike 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 scattering, 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.

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。广泛接受的神经兴奋性理论无法解释我们观察到的几种异常现象，我们已经证明这些现象也是兴奋发生所必需的。这些包括神经轴突表面原生质层的体积和温度变化，这与动作电位波形一致。我们获得了进一步的证据，表明这些变化伴随着神经细胞、纤维和突触中发生的相变，该相变是由二价阳离子（如钙）与单价阳离子（如钠和钾）的交换引起的。我们之前对灌注轴突的实验清楚地表明二价/单价阳离子交换是神经纤维可以以“全部或无”方式兴奋的机制。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引起生物分子组装体的这种变化，我们正在近乎生理条件下研究合成“仿生”阴离子聚合物凝胶中的这些过程。研究这些凝胶模型系统行为的一个优点是，与活体组织不同，它们的结构、组成及其成分之间的相互作用可以得到仔细控制。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着变化。各种基于物理化学和聚合物物理的技术，包括中子散射、渗透膨胀和机械载荷，提供了补充信息，可用于在广泛的长度尺度上研究这些生物学相关现象。这些基础研究使人们更深入地了解神经兴奋的物理机制。