T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites
T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites
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DOI：
10.1038/nn.2124
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发表时间：
2008-06-01
影响因子：
25
通讯作者：
Luthi, Anita
中科院分区：
文献类型：
--
作者：
Cueni, Lucius;Canepari, Marco;Luthi, Anita
T型钙通道（T通道）是神经元振荡（睡眠期间常见）期间节律性爆发式放电的基础。然而，受T电流选择性调节的钙依赖性效应器仍然未知。我们发现，在丘脑网状核（nRt）的树突中，细胞内钙离子浓度的升高主要由通过T通道的钙离子内流引起，并通过钙依赖性小电导（SK）型钾离子通道和钙离子摄取泵之间的竞争形成节律性爆发。振荡爆发是通过选择性激活位于树突的SK2通道而启动的，而肌浆/内质网钙 - ATP酶（SERCA）对钙离子的封存以及T通道的累积失活抑制了振荡。Sk2（ - / - ）（也称为Kcnn2）小鼠缺乏细胞振荡，在非快速眼动睡眠的脑电图中低频节律降低了三倍以上，并且睡眠受到干扰。因此，nRt树突中T通道、SK2通道和SERCA的相互作用构成了一个专门的钙信号三联体，以调节与睡眠相关的振荡动力学。
T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K1 channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2(-/-) (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.