MODULATION OF HIPPOCAMPAL K AND CA CHANNELS BY ADENOSINE

腺苷对海马 K 和 CA 通道的调节

• 批准号: 2269712
• 负责人: DAVID J MOGUL
• 金额: $ 9.15万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2269712
• 关键词: adenosine; calcium channel; electrophysiology; guinea pigs; hippocampus; microelectrodes; neural transmission; neurons; neurotransmitter receptor; potassium channel; receptor binding; receptor coupling; receptor sensitivity; synapses; voltage /patch clamp; voltage gated channel

Adenosine is produced, released, taken up, and metabolized by virtually every cell in the body. Extracellular concentrations of adenosine in the brain increase in response to conditions of increased metabolic demand such as with hypoxia, hypoglycemia, or seizure-like activity. Adenosine has been shown to depress synaptic transmission by influencing both presynaptic and postsynaptic potassium and calcium channels as well as having other systemic effects related to potassium and calcium channel modulation such as vasodilation and negative changes in cardiac inotropy and chronotropy. Adenosine is one of the major neurotransmitters in the hippocampus. Because the hippocampus is an important structure in both learning and memory and is involved in many types of epilepsies, ion channel modulation by adenosine may play a significant role in regulating hippocampal electrical activity. However, the full extent of potassium and calcium channel modulation by activation of adenosine receptors and its implications are still unknown. The goals of this grant are four-fold. First, we will investigate what types of adenosine receptors are involved in ion channel modulation in the hippocampus. Second, the identification of potassium and/or calcium channels affected by selective receptor activation and characterization of this modulation will be explored. Third, coupling mechanisms involved between receptors and channels will be determined. Finally, given that particular receptors may alter calcium and potassium channels selectively, what is the impact of these membrane changes to physiological function and, in particular, to synaptic transmission. The question of presynaptic and postsynaptic channel modifications will be studied. The experiments proposed in this grant will be performed in both acutely isolated young adult guinea pig hippocampal neurons and in the hippocampal slice preparation where appropriate. Acutely isolated neurons permit excellent space clamp control for patch clamp experiments. Electrophysiological measurements of ion channel currents will use both the whole-cell and single-channel voltage clamp configurations. synaptic transmission will be measured using the standard microelectrode and slice-patch voltage clamp techniques for recording postsynaptic potentials and currents, respectively.

腺苷是通过实际上生产，释放，取代和代谢的 体内的每个细胞。 腺苷的细胞外浓度 大脑增加了代谢需求增加的条件 与缺氧，低血糖或癫痫发作一样。 腺苷具有 被证明通过影响两种突触来降低突触传播 以及突触后钾和钙通道以及其他 与钾和钙通道调节有关的系统性作用 随着血管舒张和心脏肌力和年表的阴性变化。 腺苷是海马中主要的神经递质之一。 因为海马是学习和 内存并参与多种类型的癫痫，离子通道调制 通过腺苷可能在调节海马中起重要作用 电活动。 但是，钾和钙的全部范围 通过激活腺苷受体及其ITS频道调节 含义仍然未知。 这笔赠款的目标是四倍。 首先，我们将研究涉及哪些类型的腺苷受体 在海马中的离子通道调制中。 第二，标识 受选择受体影响的钾和/或钙通道的 将探讨此调制的激活和表征。 第三，受体和通道之间涉及的耦合机制将是 决定。 最后，鉴于特定受体可能会改变钙，并且 钾通道有选择地，这些膜的影响是什么 改变生理功能，尤其是突触 传播。 突触前和突触后通道的问题 将研究修改。 这笔赠款中提出的实验将 在两个急性分离的年轻几内亚猪海马中进行 在适当的情况下，神经元和海马切片制剂。 急性孤立的神经元允许出色的空间夹具控制斑块 夹具实验。 离子通道的电生理测量 电流将同时使用全电池和单通道电压夹 配置。 突触传输将使用标准测量 用于记录的微电极和切片点电压夹技术 突触后电势和电流。