Spence K T, Plata-Salaman C R, ffrench-Mullen J M
Department of Pharmacology, ICI Americas Inc., Wilmington, DE 19897.
Life Sci. 1991;49(26):PL235-9. doi: 10.1016/0024-3205(91)90649-v.
The neurosteroids pregnenolone (PE) and pregnenolone-sulfate (PS) have been shown to interact with the GABAA receptor in the central nervous system. In contrast, nothing is known of any possible modulation of voltage-gated calcium channels (VGCC). We have examined the interaction of PE, PS and progesterone on VGCC in acutely isolated adult guinea-pig hippocampal CA1 neurons using the whole-cell patch clamp technique. PE and PS depressed the calcium current at low micromolar concentrations (0.001-100 microM). The time to peak of the calcium current was slowed by PE and PS. The blocking action of PE and PS occurs in the presence of 10 microM picrotoxin. In contrast, progesterone had no effect on the Ca2+ current, indicating specificity for PE and PS. These results demonstrate a direct and novel membrane site of action for PE and PS, suggesting a possible role influencing brain excitability.
神经甾体孕烯醇酮（PE）和硫酸孕烯醇酮（PS）已被证明可在中枢神经系统中与GABAA受体相互作用。相比之下，关于电压门控钙通道（VGCC）是否存在任何可能的调节作用却一无所知。我们使用全细胞膜片钳技术研究了PE、PS和孕酮对急性分离的成年豚鼠海马CA1神经元中VGCC的相互作用。PE和PS在低微摩尔浓度（0.001 - 100微摩尔）时可抑制钙电流。PE和PS使钙电流达到峰值的时间延长。PE和PS的阻断作用在存在10微摩尔苦味毒的情况下依然发生。相比之下，孕酮对Ca2+电流没有影响，表明PE和PS具有特异性。这些结果证明了PE和PS存在直接且新颖的膜作用位点，提示其可能在影响脑兴奋性方面发挥作用。
