ETHANOL AND RELEASABLE STORES OF INTRACELLULAR CALCIUM

先前的研究表明，乙醇和其他麻醉剂会增加 神经元和非神经元静息细胞内钙离子浓度 纸巾。这一效应可能是酒精/麻醉剂诱导的 依赖细胞内钙的机制增加，包括 静息神经递质释放与钙依赖钾 导电性。在这份提案中。据推测，乙醇会增加 通过从细胞内释放钙来静息细胞内钙浓度 非线粒体细胞内存储部位。这家钙店也可能 由其他麻醉剂释放，但与 第二信使三磷酸肌醇释放的钙库 在受体介导的许多不同组织中产生 刺激。在拟议的研究中， 乙醇和其他麻醉剂释放的细胞内钙储存和 三磷酸肌醇释放的钙储存将在 来自大脑和肝脏以及PC12细胞的组织。潜在的机制 乙醇/麻醉剂诱导的细胞内钙释放将 也是有目共睹的。乙醇诱导心肌细胞钙释放的作用 这种细胞内的钙存储在耐受和依赖的发展中 将会被评估。这种乙醇敏感的可能的内源性调节因子 还将对钙店进行调查。一个人的存在 大脑和肝脏中储存的乙醇/麻醉剂可释放的钙表明 拟议研究的结果可能会影响到可能的 酒精滥用、成瘾和急性中毒的药物治疗 乙醇和其他麻醉剂的影响。

Previous work showed that ethanol and other intoxicant-anesthetics increase resting intracellular calcium concentrations in neuronal and non-neuronal tissues. This effect may be responsible for ethanol/anesthetic-induced increases in mechanisms dependent on intracellular calcium including resting neurotransmitter release and calcium-dependent potassium conductances. In this proposal. it is hypothesized that ethanol increases resting intracellular calcium concentrations by releasing calcium from a non-mitochondrial intracellular storage site. This calcium store may also be released by other anesthetic agents but is distinguishable from the calcium store released by inositol trisphosphate a second messenger generated in many different tissues following receptor-mediated stimulation. In the proposed studies, the relationship between the intracellular calcium stores released by ethanol and other anesthetics and the calcium stores released by inositol trisphosphate will be defined in tissues from brain and liver and in PC12 cells. Potential mechanisms of ethanol/anesthetic-induced calcium release from intracellular stores will also be distinguished. The role of ethanol-induced calcium release from this intracellular calcium store in tolerance and dependence development will be evaluated. Possible endogenous regulators of this ethanol-sensitive calcium store will also be investigated. The presence of an ethanol/anesthetic-releasable calcium store in brain and liver indicates that findings from the proposed studies may have bearing on possible pharmacological treatments for ethanol abuse and addiction and acute toxic effects of ethanol and other anesthetics.