ANESTHETICS, ISCHEMIA, AND CNS CALCIUM CHANNELS

本提案的长期目标是确定电压是否 依赖性钙通道（VDCC）是挥发性钙通道的主要作用部位。 麻醉剂，氟烷和异氟烷，以及异氟烷是否可以 减轻VDCC中观察到的缺血性变化。越 有限的目的是确定氟烷和异氟烷对 钙通道拮抗剂与VDCC的结合特性，以及 Ca 2+通过单个Ca 2+通道的运动和Ca 2+的群体 渠道Ca2+稳态和VDCC活性也已被证实。 参与缺血性CNS损伤的病理生理学， 数据表明，异氟醚可能通过作用于 VDCC。本提案将检查异氟烷、VDCC和 缺血，以确定是否改变通道密度和Ca2+流量 发生并可被异氟烷减弱。放射性配体结合测定， 用Fura 2测量分离的突触体和培养的突触体中的Ca 2+通量 神经元，并与单钙离子通道的电生理测量 将在重构膜中进行，以实现特定目标。 异氟醚及其相关化合物在治疗肺结核中的潜在优势 预防或减轻缺血性损伤将在随后的讨论中得到解决 如果上述研究的结果表明， 合理的治疗方法。

The long term objectives of this proposal are to determine whether voltage dependent Ca2+ channels (VDCC) are a major site of action of the volatile anesthetics, halothane and isoflurane, and whether isoflurane can attenuate the ischemic changes that have been observed in VDCC. The more limited aims are to define the effects of halothane and isoflurane on the binding properties of Ca2+ channel antagonists to VDCC, and on the movement of Ca2+ through single Ca2+ channels and populations of Ca2+ channels. Ca2+ homeostasis and the activity of VDCC have also been implicated in the pathophysiology of ischemic CNS damage, and preliminary data suggest that isoflurane might ameliorate CNS damage by an action on VDCC. This proposal will examine the interaction of isoflurane, VDCC, and ischemia to determine whether changes in channel density and Ca2+ flux occur and can be attenuated by isoflurane. Radioligand binding assays, Ca2+ flux measurements with fura 2 in isolated synaptosomes and cultured neurons, and with electrophysiologic measurements of single Ca2+ channels in reconstituted membranes will be performed to achieve the specific aims. The potential therapeutic advantage of isoflurane and related compounds in preventing or lessening ischemic damage would be addressed in subsequent proposals if findings derived from the described studies suggest a rational therapeutic approach.