Daniell L C, Harris R A
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
Alcohol Clin Exp Res. 1991 Mar;15(2):224-8. doi: 10.1111/j.1530-0277.1991.tb01860.x.
Our previous work showed that ethanol increases the resting intracellular free calcium concentration (CAi) in synaptosomes and releases calcium from an inositol trisphosphate (IP3)-insensitive calcium store of brain microsomes. In this report, we investigated the effects of chronic ethanol treatment and selective breeding for hypnotic sensitivity to ethanol on IP3 and ethanol-stimulated calcium release from brain and liver microsomes. Chronic ethanol treatment did not alter IP3-stimulated calcium release from brain microsomes or ethanol-stimulated calcium release from brain or liver microsomes. Chronic ethanol treatment increased the spontaneous release of calcium from brain but not liver microsomes. In microsomes isolated from cerebellum or cerebral cortex of long-sleep (LS) and short-sleep (SS) mice, ethanol and IP3 released calcium in a concentration dependent manner. The amount of calcium released by ethanol and IP3 was larger in microsomes isolated from cerebellum than microsomes from cerebral cortex. However, the amount of calcium released by ethanol and IP3 did not differ between the two lines in either brain area. These results do not support the idea that the hypnotic effects of ethanol are due to ethanol-induced calcium release from a nonmitochondrial intracellular calcium store in brain tissue. The development of ethanol tolerance and dependence also does not appear to be associated with altered ability of ethanol to release calcium from non-mitochondrial intracellular stores; however, effects of chronic ethanol exposure on spontaneous release of intracellular calcium could alter neuronal function in ethanol dependence.
我们之前的研究表明，乙醇可增加突触体中静息细胞内游离钙浓度（CAi），并从脑微粒体的肌醇三磷酸（IP3）不敏感钙库中释放钙。在本报告中，我们研究了慢性乙醇处理以及对乙醇催眠敏感性进行选择性育种对IP3和乙醇刺激的脑及肝微粒体钙释放的影响。慢性乙醇处理并未改变IP3刺激的脑微粒体钙释放或乙醇刺激的脑或肝微粒体钙释放。慢性乙醇处理增加了脑而非肝微粒体的钙自发释放。在从长睡眠（LS）和短睡眠（SS）小鼠的小脑或大脑皮质分离的微粒体中，乙醇和IP3以浓度依赖方式释放钙。乙醇和IP3释放的钙量在从小脑分离的微粒体中比从大脑皮质分离的微粒体中更大。然而，在任一脑区，乙醇和IP3释放的钙量在两个品系之间并无差异。这些结果并不支持乙醇的催眠作用是由于乙醇诱导脑组织中非线粒体细胞内钙库释放钙这一观点。乙醇耐受性和依赖性的发展似乎也与乙醇从非线粒体细胞内储存释放钙的能力改变无关；然而，慢性乙醇暴露对细胞内钙自发释放的影响可能会改变乙醇依赖性中的神经元功能。
