MODULATION OF HIPPOCAMPAL K AND CA CHANNELS BY ADENOSINE

腺苷的产生、释放、吸收和代谢实际上是由 身体里的每一个细胞。腺苷在细胞外的浓度 大脑对代谢需求增加等条件的反应增加 如缺氧、低血糖或癫痫样活动。腺苷有 被证明通过影响两个突触前信号来抑制突触传递 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全身效应 作为血管扩张和负性心脏变力和变时性改变。 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学习中的一个重要结构 记忆与多种类型癫痫有关，离子通道调制 腺苷可能在海马区的调节中起重要作用 电活动。然而，钾和钙的全部含量 腺苷受体激活对通道的调制作用及其机制 其影响仍不得而知。这笔赠款的目标有四个。 首先，我们将调查哪些类型的腺苷受体参与其中 在海马体的离子通道调制中。第二，身份识别 选择性受体对钾和/或钙通道的影响 将探索这种调制的激活和表征。 第三，受体和通道之间涉及的耦合机制将是 下定决心。最后，鉴于特定的受体可能改变钙和 选择性钾通道，对这些膜有什么影响 生理功能的变化，特别是突触的变化 变速箱。突触前和突触后通道的问题 将对修改进行研究。这项拨款中提议的实验将 在急性分离的幼年豚鼠海马区 并在适当的情况下在海马区切片制备。 急性分离的神经元允许出色的空间钳制控制用于贴片 钳制实验。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钳位 配置。突触传递将使用标准来测量 微电极和薄片膜片电压钳记录技术 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.