MODULATION OF HIPPOCAMPAL K AND CA CHANNELS BY ADENOSINE

腺苷的产生、释放、吸收和代谢几乎是由 身体里的每一个细胞。 细胞外腺苷浓度 大脑增加，以响应代谢需求增加的条件， 如缺氧、低血糖或类似糖尿病的活动。 腺苷具有 通过影响突触前神经元和突触后神经元， 以及突触后钾和钙通道，以及其他 与钾和钙通道调节相关的全身效应， 如血管舒张和心脏变力性和变时性的负性变化。 腺苷是海马体中的主要神经递质之一。 因为海马体是学习和记忆的重要结构， 记忆和参与许多类型的癫痫，离子通道调制 可能在调节海马神经元凋亡中起重要作用。 电活动。 然而，钾和钙的全部含量 通过腺苷受体的激活调节通道及其 其影响尚不清楚。 这项补助金的目标有四个方面。 首先，我们将研究参与的腺苷受体类型 海马体离子通道的调节。 第二，识别 受选择性受体影响的钾和/或钙通道 将探索这种调节的激活和表征。 第三，受体和通道之间的耦合机制将被研究。 测定 最后，考虑到特定的受体可能会改变钙和 钾通道的选择性，这些膜的影响是什么？ 生理功能的变化，特别是突触 传输 突触前和突触后通道的问题 将进行修改研究。 这项资助中提出的实验将 在急性分离的年轻成年豚鼠海马 神经元和适当的海马切片制备。 急性分离的神经元允许对膜片钳的良好的空间钳控制 夹钳实验 离子通道的电生理测量 电流将使用全细胞和单通道电压钳 配置. 突触传递将使用标准的 微电极和薄片-膜片电压钳技术 突触后电位和电流。

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.