CALCIUM CURRENT POTENTIATION IN HIPPOCAMPAL NEURONS

海马神经元的钙电流增强

• 批准号: 2519971
• 负责人: Mark R. Plummer
• 金额: $ 19.59万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2519971
• 关键词: action potentials; calcium channel; dihydropyridines; electrophysiology; hippocampus; laboratory rat; neural plasticity; neurotransmitters; protein kinase; second messengers; tissue /cell culture; voltage /patch clamp; voltage gated channel

The aim of this project is to examine the elementary properties of a unique kind of calcium channel that responds to transient depolarizations with long-lasting increases in activity. Interestingly, we have observed this type of calcium channel activity in hippocampal neurons, but not in neurons of the sympathetic ganglia, suggesting that this voltage- dependent, long-term activation, or potentiation, may contribute to some aspect of the complex synaptic plasticity that has been observed in the hippocampus. At present, too little is known about this channel to speculate on its specific functions, although the possibilities are quite diverse, ranging from enhanced neuronal excitability to regulation of gene expression. For example, calcium channels of this type have been implicated in aging- related learning deficits. It is, therefore, critical to determine the precise biophysical characteristics of this potentiated activity under standard and physiologically-relevant conditions to make comparisons with other known calcium channel types and to gain insights into the effects this activity would have on neurons in situ. Furthermore, by determining how channel responsiveness is altered through the action of second messenger systems and by learning whether specific neurotransmitters can activate these same pathways in hippocampal neurons, important insights into the dynamic regulation of this calcium channel potentiation can be obtained. Moreover, by using a combination of kinetic modeling and related experimental protocols, it will be possible to gain a fundamental understanding of the mechanisms that underlie long-lasting calcium channel activity. To accomplish these goals, single-channel and whole-cell patch clamp recordings will be made from hippocampal neurons. A variety of stimulation protocols and recording conditions will be used to determine the time course and voltage-dependence of the potentiated activity. In addition, a collaborative effort to identify the molecular composition of this calcium channel will be initiated during the time covered by this grant application. By systematically studying a calcium channel with such intriguing properties, we will establish the strong foundation necessary to understand the functional role and clinical relevance of calcium channel potentiation in the hippocampus.

该项目的目的是检查a的基本属性 响应瞬时去极化的独特钙通道 随着活动的持久增加。 有趣的是，我们观察到 海马神经元中存在这种类型的钙通道活性，但在 交感神经节的神经元，表明该电压 依赖的、长期的激活或增强，可能有助于某些 在观察到的复杂突触可塑性方面 海马体。 目前，人们对该频道知之甚少，无法推测其 特定的功能，尽管可能性多种多样，范围 从增强神经元兴奋性到调节基因表达。 为了 例如，这种类型的钙通道与衰老有关 相关的学习缺陷。 因此，确定 这种增强活性的精确生物物理特征 标准和生理相关条件进行比较 其他已知的钙通道类型并深入了解其影响 这种活动会对原位神经元产生影响。 此外，通过确定 如何通过第二个动作改变通道响应能力 信使系统并通过了解特定的神经递质是否可以 激活海马神经元中的这些相同的通路，重要的见解 进入这种钙通道增强的动态调节可以 获得。 此外，通过结合使用动力学建模和 相关的实验方案，将有可能获得基本的 了解持久钙通道的机制 活动。 为了实现这些目标，单通道和全细胞膜片钳 录音将由海马神经元进行。 各种 刺激方案和记录条件将用于确定 增强活性的时间进程和电压依赖性。 在 此外，合作努力确定的分子组成 该钙通道将在该时间范围内启动 拨款申请。 通过系统地研究钙通道 有趣的特性，我们将建立必要的坚实基础 了解钙的功能作用和临床相关性 海马体中的通道增强。

项目成果

Sustained activation of hippocampal Lp-type voltage-gated calcium channels by tetanic stimulation.

通过强直刺激持续激活海马 Lp 型电压门控钙通道。

• DOI: 10.1523/jneurosci.20-13-04786.2000
• 发表时间: 2000
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Schjott,JM;Plummer,MR
• 通讯作者: Plummer,MR

cAMP-dependent enhancement of dihydropyridine-sensitive calcium channel availability in hippocampal neurons.

海马神经元中二氢吡啶敏感钙通道可用性的 cAMP 依赖性增强。

• DOI: 10.1523/jneurosci.17-14-05334.1997
• 发表时间: 1997
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Kavalali,ET;Hwang,KS;Plummer,MR
• 通讯作者: Plummer,MR

The neuronal beta 4 subunit increases the unitary conductance of L-type voltage-gated calcium channels in PC12 cells.

神经元 β4 亚基增加 PC12 细胞中 L 型电压门控钙通道的单一电导。

• DOI: 10.1074/jbc.m302059200
• 发表时间: 2003
• 期刊: The Journal of biological chemistry
• 作者: Schjött,JessicaM;Hsu,Shu-Chan;Plummer,MarkR
• 通讯作者: Plummer,MarkR

Multiple voltage-dependent mechanisms potentiate calcium channel activity in hippocampal neurons.

多种电压依赖性机制增强海马神经元中的钙通道活性。

• DOI: 10.1523/jneurosci.16-03-01072.1996
• 发表时间: 1996
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience.
• 作者: Kavalali,ET;Plummer,MR
• 通讯作者: Plummer,MR