Mullikin-Kilpatrick D, Treistman S N
Department of Pharmacology, University of Massachusetts Medical Center, Worcester 01655, USA.
Alcohol Alcohol Suppl. 1993;2:385-9.
In this paper, we describe the effects of both acute and chronic ethanol exposure on voltage-activated calcium channels in undifferentiated pheochromocytoma (PC12) cells. Calcium uptake and calcium mediated release studies have shown that calcium channels in these cells are sensitive to ethanol (Messing et al., 1986, Rabe and Weight, 1988, Koski et al., 1991 and Grant et al. in press). Using whole-cell patch clamp techniques, we show that the electrical properties of the channels are very sensitive to acute ethanol. Calcium currents were significantly inhibited by 25 mM acute ethanol and this effect was reversible. In contrast to the reduction of current seen with acute ethanol exposure, chronic ethanol exposure of the cells resulted in a significant increase in calcium current. Examination of whole-cell calcium currents suggested the development of tolerance to ethanol in PC12 cells. Currents evoked from cells exposed to chronic ethanol were inhibited less by acute ethanol than currents from cells not exposed to chronic ethanol. Collectively, these data demonstrate that calcium channels in PC12 cells are sensitive targets for both acute and chronic ethanol.
在本文中,我们描述了急性和慢性乙醇暴露对未分化嗜铬细胞瘤(PC12)细胞中电压激活钙通道的影响。钙摄取和钙介导的释放研究表明,这些细胞中的钙通道对乙醇敏感(梅辛等人,1986年;拉贝和韦特,1988年;科斯基等人,1991年;格兰特等人,即将发表)。使用全细胞膜片钳技术,我们发现通道的电学特性对急性乙醇非常敏感。25 mM急性乙醇可显著抑制钙电流,且这种效应是可逆的。与急性乙醇暴露导致的电流减少相反,细胞慢性乙醇暴露导致钙电流显著增加。对全细胞钙电流的检测表明PC12细胞对乙醇产生了耐受性。与未暴露于慢性乙醇的细胞的电流相比,暴露于慢性乙醇的细胞所诱发的电流受急性乙醇的抑制作用较小。总体而言,这些数据表明PC12细胞中的钙通道是急性和慢性乙醇的敏感靶点。