Inhibition of T-type calcium current in the reticular thalamic nucleus by a novel neuroactive steroid
Inhibition of T-type calcium current in the reticular thalamic nucleus by a novel neuroactive steroid
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DOI：
10.1196/annals.1403.006
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Todorovic, Slobodan M.
中科院分区：
文献类型：
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作者：
Joksovic, Pavle M.;Covey, Douglas F.;Todorovic, Slobodan M.
丘脑网状核（nRT）的神经元作为一个重要的抑制门，控制丘脑皮质感觉信号的运输和睡眠，觉醒和癫痫的状态。nRT中的T-型钙通道在这些神经元的阈下兴奋性中起着至关重要的作用，但以前没有研究过神经活性类固醇对它们的调节。在这里，我们探讨了（3 β，5 β，17 β）-3-羟基雄甾烷-17-腈（3 β-OH），一种新的神经活性类固醇对T型电流记录从nRT神经元在完整的年轻大鼠脑切片的影响。我们在电压钳实验中发现，3 β-OH有效地和可逆地降低T型Ca 2+电流的幅度和稳定的通道的非活性状态。在电流钳实验中，3 β-OH显著降低了负膜电位的动作电位放电频率，并最小程度地改变了被动膜特性。我们的研究结果表明，5 β-还原的神经活性类固醇，通过抑制T-型钙电流和减少尖峰放电的nRT神经元的机制，可能是重要的代理人在控制感官信息处理在生理条件下，可能是病理性的大脑状态与细胞兴奋性增加，如癫痫和/或组织缺血/缺氧。
Neurons of the nucleus reticularis of the thalamus (nRT) serve as an important inhibitory gate that controls trafficking of thalamocortical sensory signals and states of sleep, arousal, and epilepsy. T-type calcium channels in nRT play a crucial role in the subthreshold excitability of these neurons, but their modulation by neuroactive steroids has not been previously studied. Here we explored the effect of (3 beta,5 beta,17 beta)-3-hydroxyandrostane-17-carbonitrile (3 beta-OH), a novel neuroactive steroid on T-type currents recorded from nRT neurons in intact brain slices of young rats. We found in voltage-clamp experiments that 3 beta-OH potently and reversibly decreased T-type Ca2+ current amplitude and stabilized inactive states of the channels. In current-clamp experiments, 3 beta-OH significantly decreased the frequency of action potential firing from negative membrane potentials and minimally changed passive membrane properties. Our results indicate that 5 beta-reduced neuroactive steroids, through the mechanisms of inhibition of T-type Ca2+ currents and diminished spike firing in nRT neurons, may be important agents in control of sensory information processing in physiological conditions and possibly pathological brain states associated with increased cellular excitability such as epilepsy and/or tissue ischemia/hypoxia.