Hesen W, Joëls M
Graduate School for the Neurosciences, Department of Experimental Zoology, Faculty of Biology, University of Amsterdam, The Netherlands.
Brain Res. 1993 Nov 5;627(1):159-67. doi: 10.1016/0006-8993(93)90760-k.
Pyramidal neurons in the rat CA1 hippocampal area contain membrane receptors for acetylcholine but also intracellular receptors for the adrenal corticosteroid hormone corticosterone, i.e., mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). In this in vitro study we investigated if occupation of MRs or GRs affects the responsiveness of CA1 pyramidal neurons to the cholinergic analogue carbachol. In slices from adrenally intact rats, where probably most of the MRs and a considerable degree of the GRs were occupied, carbachol (0.1-30 microM) induced a dose-dependent: (i) depolarization; (ii) reduction of the afterhyperpolarization and spike frequency accommodation associated with depolarizing current pulses; and (iii) reduction of the synaptically evoked EPSP, slow IPSP and (with higher doses) the fast IPSP. The carbachol responses in slices from adrenalectomized (ADX) rats, where both MRs and GRs are unoccupied, were generally similar to the responses in the adrenally intact controls. However, neurons recorded in slices from ADX rats 1-4 h after a brief (20 min) application of 3 nM aldosterone, thus predominantly occupying MRs, showed a significant reduction of the carbachol (1 microM) induced depolarization, when compared to the adrenally intact group. By contrast, neurons recorded in ADX slices treated with 30 nM corticosterone, inducing simultaneous activation of MRs and GRs, displayed significantly larger carbachol-evoked depolarizations (1 and 3 microM) than neurons in the three previous experimental groups. Carbachol-induced actions on the afterhyperpolarization, accommodation and synaptically evoked responses did not consistently depend on steroid receptor occupation.(ABSTRACT TRUNCATED AT 250 WORDS)
大鼠CA1海马区的锥体神经元含有乙酰胆碱膜受体，也含有肾上腺皮质类固醇激素皮质酮的细胞内受体，即盐皮质激素受体（MRs）和糖皮质激素受体（GRs）。在这项体外研究中，我们调查了MRs或GRs的占据是否会影响CA1锥体神经元对胆碱能类似物卡巴胆碱的反应性。在肾上腺完整大鼠的切片中，可能大部分MRs和相当程度的GRs被占据，卡巴胆碱（0.1 - 30微摩尔）诱导剂量依赖性：（i）去极化；（ii）与去极化电流脉冲相关的超极化后电位和动作电位频率适应性降低；（iii）突触诱发的兴奋性突触后电位、慢抑制性突触后电位以及（高剂量时）快抑制性突触后电位降低。肾上腺切除（ADX）大鼠切片中的卡巴胆碱反应，其中MRs和GRs均未被占据，通常与肾上腺完整对照组的反应相似。然而，在短暂（20分钟）应用3纳摩尔醛固酮后1 - 4小时从ADX大鼠切片中记录的神经元，因此主要占据MRs，与肾上腺完整组相比，显示出卡巴胆碱（1微摩尔）诱导的去极化显著降低。相比之下，用30纳摩尔皮质酮处理的ADX切片中记录的神经元，诱导MRs和GRs同时激活，显示出比前三个实验组的神经元更大的卡巴胆碱诱发的去极化（1和3微摩尔）。卡巴胆碱对超极化后电位、适应性和突触诱发反应的作用并不一致地依赖于类固醇受体的占据。（摘要截断于250字）
