Karst H, Wadman W J, Joëls M
Department of Experimental Zoology, University of Amsterdam, The Netherlands.
Brain Res. 1994 Jun 27;649(1-2):234-42. doi: 10.1016/0006-8993(94)91069-3.
Pyramidal CA1 neurons in the rat hippocampus contain mineralocorticoid (MRs) and glucocorticoid receptors (GRs) for corticosterone, which, in activated form, act as transcription factors of the genome. The relative MR and GR occupation changes throughout the day, with predominant MR occupation under rest in the morning and additional GR occupation in the evening and after stress. We examined the effect of MR and GR activation on Ca currents in hippocampal slices from adrenalectomized (ADX) rats under whole-cell voltage-clamp conditions. In slices from ADX rats, where MRs and GRs are unoccupied, Ca currents (particularly in the low-voltage range) were larger than in neurons from the sham-operated controls; these effects became apparent with a delay of > or = 3 days after ADX. Selective occupation of MRs in tissue from ADX rats greatly (by 70%) and persistently (up to 3 h) reduced transient but also sustained Ca conductances. Voltage dependency and kinetic properties of the currents were not affected. Occupation of GRs as well as MRs by corticosterone (30 nM) resulted in relatively large Ca currents, comparable to those recorded in tissue from mildly stressed sham-operated control animals. Interestingly, exclusive occupation of GRs with 30 nM RU 28362 was not sufficient to induce large Ca currents. The data suggest that the changes in MR and GR occupation throughout the day, related to circadian and stress-induced corticosterone release, are linked to marked alterations in Ca currents, with small Ca currents in the morning and large currents in the evening or after stress.(ABSTRACT TRUNCATED AT 250 WORDS)
大鼠海马体中的锥体细胞层CA1神经元含有皮质酮的盐皮质激素受体（MRs）和糖皮质激素受体（GRs），这些受体在激活状态下作为基因组的转录因子发挥作用。MR和GR的相对占有率在一天中会发生变化，早晨休息时主要是MR被占据，晚上和应激后则有额外的GR被占据。我们在全细胞膜片钳条件下，研究了MR和GR激活对肾上腺切除（ADX）大鼠海马切片中钙电流的影响。在ADX大鼠的切片中，MRs和GRs未被占据，钙电流（特别是在低电压范围内）比假手术对照组的神经元中的钙电流更大；这些效应在ADX后≥3天出现延迟才变得明显。选择性占据ADX大鼠组织中的MRs会大幅（70%）且持续（长达3小时）降低瞬时和持续的钙电导。电流的电压依赖性和动力学特性不受影响。皮质酮（30 nM）同时占据GRs和MRs会导致相对较大的钙电流，与轻度应激的假手术对照动物组织中记录的电流相当。有趣的是，仅用30 nM RU 28362占据GRs不足以诱导出大的钙电流。数据表明，与昼夜节律和应激诱导的皮质酮释放相关的MR和GR占有率在一天中的变化，与钙电流的显著改变有关，早晨钙电流小，晚上或应激后钙电流大。（摘要截短于250字）
