ADENOSINE MODULATION OF SYNAPTIC TRANSMISSION

众所周知，腺苷对哺乳动物有重大影响。 中枢神经系统。这种腺苷效应，至少在一定程度上似乎 通过其对突触传递的影响来调节。我们有 最近发现腺苷选择性地减弱兴奋性 突触传递，对抑制作用无明显影响 它的传播似乎与其广义的 抗抑郁作用。此外，腺苷似乎扮演着至关重要的角色。 在脑缺血和癫痫的病理生理学方面。鉴于不断增长的 这两种病理性腺苷的兴奋性毒性概念 似乎是一种诱人的药剂，可以对抗这两种神经系统 侮辱。这项提案的总体目标是确定 腺苷调节兴奋性突触传递的机制 并证明与A2型相关的腺苷效应 腺苷受体。长期目标是提供一些 腺苷在正常神经生理中作用的研究进展 常见神经疾病的过程和病理生理学。 原代分离的大鼠海马区培养将联合使用 采用标准的全细胞膜片钳记录技术。这个 这项建议的具体目的是：1)研究和比较效果 腺苷对兴奋性神经元和抑制性神经元的作用 腺苷电流的特性及其对钙的影响 电导，2.比较GABA/β和腺苷的药理作用 研究内源性腺苷对体外培养细胞的影响。 海马细胞。

Adenosine has been known to have significant effects on mammalian central nervous system. This adenosine effect, at least in part seems to be mediated by its effect on the synaptic transmission. We have recently discovered that adenosine selectively attenuates excitatory synaptic transmission and had no significant effect on inhibitory transmission which seems to be consistent with its generalized depressant effect. Furthermore, adenosine seems to play a critical role in pathophysiology of ischemia and epilepsy. In light of the growing concept of excitotoxicity in these two pathological processed adenosine seems to be an attractive agent counteracting these two neurological insults. The overall objective of this proposal is to determine the mechanism by which adenosine modulates excitatory synaptic transmission and to demonstrate the possible adenosine effect linked to A2 type adenosine receptor. The long term objective is to provide some information on adenosine's role in the physiology of normal neural processes and the pathophysiology of common neurological disorders. Primary dissociated rat hippocampal cultures will be used in conjunction with standard whole-cell, patch-clamp recording techniques. The specific aims of this proposal are: 1) to study and compare the effect of adenosine on identified excitatory and inhibitory neurons by characterizing the adenosine current and its effect on calcium conductance, 2. to compare the pharmacology of GABA/beta and adenosine effects, 3. to study the effect of endogenous adenosine in cultured hippocampal cells.