SODIUM PUMP AND REGULATION OF NEURONAL EXCITABILITY

钠泵(Na+/K+-ATPase)在细胞中几乎无处不在，主要服务于 与跨膜Na+、K+维持相关的多种功能 渐变。尽管它的重要性通常主要被认为是与 就其体内平衡作用而言，钠泵实际上是一类酶 异质分布在大脑中，并受 许多内生因素，表明存在广泛的 Na+泵功能。这个项目试图检验普遍的假设 钠泵的调节提供了一种重要的机制 神经元兴奋性的控制。可逆式部分Na+泵 将使用抑制和刺激，与 电生理技术，在大鼠海马片上的研究 Na+泵影响兴奋性的机制。少校 重点放在部分钠泵抑制引起的癫痫样活动上。 项目的具体目标将检验以下假设：1.PPI 选择性减少突触引起癫痫样活动 抑制力。2.通过突触通道的离子流量可导致钠泵 激活。3.PPI诱导CA3兴奋性持续增加 通过一个类似LTP的过程。4.PPI导致了LTD式的抑制 CA1区的突触反应。5.PPI抑制突发放电过程 取自幼年动物的切片。 钠泵功能障碍被认为与许多疾病状态有关， 包括癫痫，但关于分子的丰富信息 钠离子泵的生物学和生物化学是无与伦比的 对其生理作用的理解。这项提议是迈出的一步 来填补这一空白。

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.