Werkman T R, Van der Linden S, Joëls M
Department of Experimental Zoology, University of Amsterdam, The Netherlands.
Neuroscience. 1997 Jun;78(3):663-72. doi: 10.1016/s0306-4522(96)00624-0.
Consequences of corticosteroid receptor activation on voltage-dependent Na+ conductances were studied in acutely dissociated CA1 hippocampal neurons. This preparation was selected because of the compact electrotonic properties of dissociated neurons, allowing reliable voltage-clamp of the large and fast Na+ currents. The Na+ currents were studied in (i) neurons of adrenalectomized animals (no steroid receptors occupied), (ii) neurons from tissue of adrenalectomized rats treated in vitro with corticosterone and the glucocorticoid receptor antagonist RU38486 (selectively occupying the mineralocorticoid receptor), (iii) corticosterone-treated neurons of adrenalectomized animals (occupying both the mineralocorticoid and glucocorticoid receptors) and (iv) neurons of sham-operated animals. Activation and steady-state inactivation properties of the Na+ current recorded in neurons of adrenalectomized animals were slightly shifted (3-5 mV) to hyperpolarized potentials as compared to the Na+ currents from neurons of the other experimental groups. Furthermore, the removal from inactivation of the Na+ current in the group of neurons of adrenalectomized animals was relatively slow. Although small, these effects could influence neuronal properties like action potential generation and accommodation. Under the present experimental conditions, no apparent differences were seen between cells with predominant mineralocorticoid receptor activation and cells where both mineralocorticoid and glucocorticoid receptors were occupied. In contrast to Na+ currents, voltage-dependent Ca2+ currents displayed no steroid-dependent shifts in voltage-dependent properties. However, Ca2+ current amplitudes were increased by approximately 160% in CA1 neurons of adrenalectomized animals as compared to Ca2+ currents from neurons of the other experimental groups. We conclude that corticosteroid receptor activation affects various properties of voltage-dependent Na+ and Ca2+ conductances in CA1 neurons, indicating that the steroid receptors are involved in the modulation of neuronal excitability in these cells.
在急性分离的海马CA1神经元中研究了皮质类固醇受体激活对电压依赖性钠电导的影响。选择这种制备方法是因为分离的神经元具有紧密的电紧张特性，能够可靠地电压钳制大的快速钠电流。在以下几种情况下研究钠电流：（i）肾上腺切除动物的神经元（无类固醇受体被占据）；（ii）来自肾上腺切除大鼠组织的神经元，体外给予皮质酮和糖皮质激素受体拮抗剂RU38486（选择性占据盐皮质激素受体）；（iii）肾上腺切除动物经皮质酮处理的神经元（同时占据盐皮质激素和糖皮质激素受体）；（iv）假手术动物的神经元。与其他实验组神经元的钠电流相比，肾上腺切除动物神经元记录的钠电流的激活和稳态失活特性略微向超极化电位偏移（3 - 5 mV）。此外，肾上腺切除动物神经元组中钠电流从失活状态恢复的过程相对较慢。尽管这些影响较小，但可能会影响神经元特性，如动作电位的产生和适应性。在当前实验条件下，主要激活盐皮质激素受体的细胞和同时占据盐皮质激素和糖皮质激素受体的细胞之间未观察到明显差异。与钠电流不同，电压依赖性钙电流在电压依赖性特性方面未表现出类固醇依赖性偏移。然而，与其他实验组神经元的钙电流相比，肾上腺切除动物CA1神经元的钙电流幅度增加了约160%。我们得出结论，皮质类固醇受体激活会影响CA1神经元中电压依赖性钠和钙电导的各种特性，表明类固醇受体参与了这些细胞中神经元兴奋性的调节。
