NEURONS AND GLIA IN VITRO

影响心力衰竭发生和终止的生理因素 大脑皮层癫痫放电对了解 这一过程的病理生理学。细胞外离子浓度的变化 大脑影响神经元的行为，并可作为 癫痫样放电；事实上，这种情况已经被证明是 胞外[K+]。细胞外pH(Pho)最近被证明是 直接影响神经元的兴奋性并调节其作用 N-甲基-D-天冬氨酸(NMDA)受体的兴奋性神经递质； 具体地说，酸移降低了兴奋性，阻断了NMDA电流。 此外，pho的巨大而持久的变化伴随着剧烈的变化。 神经活动。活性依赖的磷光体向酸性方向移动 似乎至少部分是由神经胶质细胞介导的。这些 观察结果提示了癫痫放电受到影响的假设 通过pho和依赖活性的胞外酸化，介导在 部分由胶质细胞组成，起到负反馈机制的作用 癫痫样放电。这些假说将使用新皮质和 海马脑片和离子敏感微电极。的作用 神经胶质细胞在调节胞外酸化中的作用将用 离子敏感微电极和“纯神经胶质”大鼠视神经。 细胞内pH调节的某些方面可能有助于 细胞外酸化将在培养的神经胶质细胞和 用显微荧光法测定神经元。拟议的研究代表了一项 继续研究哺乳动物的基本生理特性 胶质细胞与脑的离子调节和体积调节的关系 细胞外空间。这些研究将提供有用的新信息 关于PHO在大脑中波动的机制 PHO作为过度神经活动的调节器的重要性 癫痫。

Physiological factors which influence the initiation and cessation of cortical epileptic discharge are important in understanding the pathophysiology of this process. Extracellular ion concentrations in the brain influence neuronal behavior and could serve as modulators of epileptic discharge; in fact, this has been shown to be the case for extracellular [K+]. Extracellular pH (pHo) has recently been shown to directly influence neuronal excitability and to modulate the action of excitatory neurotransmitters at the N-methyl D-Aspartate (NMDA) receptor; specifically, acid shifts decrease excitability and block NMDA currents. Furthermore, large and long-lasting changes in pHo occur with intense neural activity. Activity-dependent pHo shifts in the acid direction appear to be mediated, at least in part, by glial cells. These observations prompt the hypotheses that epileptic discharge is influenced by pHo and that activity-dependent extracellular acidification, mediated in part by glial cells, acts as a negative feedback mechanism to inhibit epileptic discharge. These hypotheses will be tested using neocortical and hippocampal brain slices and ion-sensitive microelectrodes. The role of glial cells in mediating extracellular acidification will be studied using ion-sensitive microelectrodes and the 'pure glial' rat optic nerve. Aspects of intracellular pH regulation that might contribute to extracellular acidification will be analyzed in cultured glial cells and neurons using microfluorometry. The proposed research represents a continuation of studies on the basic physiological properties of mammalian glial cells, in relationship to the ionic and volume regulation of brain extracellular space. These studies will provide useful new information about the mechanisms of pHo fluctuations in the brain while assessing the importance of pHo as a modulator of the excessive neural activity seen in epilepsy.