SODIUM PUMP AND REGULATION OF NEURONAL EXCITABILITY

钠泵（Na+/K+-ATP酶）几乎普遍存在于细胞中， 与维持跨膜Na+和K+相关的多种功能 梯度。 虽然它的重要性往往被认为主要是在关系 Na+泵实际上是一个酶家族， 在大脑中分布不均匀，并受到调节， 许多内生因素，表明存在广泛的 Na+泵功能。这个项目旨在测试一般假设 Na+泵的调节提供了一个重要的机制， 控制神经元的兴奋性。 可逆部分Na+泵 抑制和刺激将与 电生理技术，在大鼠海马脑片上进行研究 Na+泵影响兴奋性的机制。主要 重点是部分钠泵抑制诱导的癫痫样活动。 本项目的具体目标将检验以下假设：1. PPI 通过选择性地减少突触神经元， 抑制作用 2.通过突触通道的离子流可导致Na泵 activation. 3. PPI诱导CA 3兴奋性持续增加 通过类似LTP的过程。 4. PPI引起类似LTD的抑制， CA 1的突触反应。 5. PPI抑制猝发放电过程 在幼年动物的切片中。 Na+泵功能障碍与许多疾病状态有关， 包括癫痫，但是大量的分子信息 Na+泵的生物学和生物化学与可比较的 了解其生理作用。 这个提议是一个步骤 填充差距。

The sodium pump (Na+/K+-ATPase) is nearly ubiquitous in cells and serves diverse functions related to maintenance of transmembrane Na+ and K+ gradients. Although its importance is often regarded mainly in relation to its homeostatic roles, the Na+ pump is actually a family of enzymes heterogeneously distributed in the brain and subject to regulation by many endogenous factors, suggesting the existence of a broad range of Na+ pump functions. This project seeks to test the general hypothesis that regulation of the Na+ pump provides an important mechanism for the control of neuronal excitability. Reversible, partial Na+ pump inhibition and stimulation will be used, in conjunction with electrophysiological techniques, in the rat hippocampal slice to study the mechanisms by which the Na+ pump affects excitability. The major focus is on epileptiform activity induced by partial Na pump inhibition. Specific aims of the project will test the following hypotheses: 1. PPI causes epileptiform activity by selectively reducing synaptic inhibition. 2. Ion fluxes through synaptic channels can lead to Na pump activation. 3. PPI induces a persistent increase in excitability in CA3 through an LTP-like process. 4. PPI causes an LTD-like suppression of synaptic responses in CA1. 5. PPI suppresses burst discharge processes in slices from juvenile animals. Na+ pump dysfunction has been implicated in a number of disease states, including epilepsy, but the wealth of information on the molecular biology and biochemistry of the Na+ pump is not matched by a comparable understanding of its physiological roles. This proposal is a step towards filling the gap.