Lee Jungryun, Kim Daesoo, Shin Hee-Sup
Center for Calcium and Learning, Division of Life Sciences, Korea Institute of Science and Technology, Seoul 136-791, Korea.
Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18195-9. doi: 10.1073/pnas.0408089101. Epub 2004 Dec 15.
T-type calcium channels have been implicated as a pacemaker for brain rhythms during sleep but their contribution to behavioral states of sleep has been relatively uncertain. Here, we found that mice lacking alpha1(G) T-type Ca(2+) channels showed a loss of the thalamic delta (1-4 Hz) waves and a reduction of sleep spindles (7-14 Hz), whereas slow (<1 Hz) rhythms were relatively intact, when compared with the wild-type during urethane anesthesia and non-rapid eye movement (NREM) sleep. Analysis of sleep disturbances, as defined by the occurrence of brief awakening (BA) episodes during NREM sleep, revealed that mutant mice exhibited a higher incidence of BAs of >16 sec compared with the wild-type, whereas no difference was seen in BAs of <16 sec between the two genotypes. These results are consistent with the previous idea of the distinct nature of delta oscillations and sleep spindles from cortically generated slow waves. These results also suggest that the alpha1(G)-subunit of T-type calcium channels plays a critical role in the genesis of thalamocortical oscillations and contributes to the modulation of sleep states and the transition between NREM sleep and wake states.
T型钙通道被认为是睡眠期间脑节律的起搏器,但其对睡眠行为状态的作用相对不确定。在此,我们发现,与野生型小鼠相比,缺乏α1(G) T型钙通道的小鼠在氨基甲酸乙酯麻醉和非快速眼动(NREM)睡眠期间,丘脑δ波(1-4赫兹)消失,睡眠纺锤波(7-14赫兹)减少,而慢波(<1赫兹)相对完整。通过分析NREM睡眠期间短暂觉醒(BA)发作所定义的睡眠障碍,发现突变小鼠与野生型相比,>16秒的BA发生率更高,而两种基因型之间<16秒的BA无差异。这些结果与之前关于δ振荡和睡眠纺锤波与皮质产生的慢波性质不同的观点一致。这些结果还表明,T型钙通道的α1(G)亚基在丘脑皮质振荡的发生中起关键作用,并有助于调节睡眠状态以及NREM睡眠和觉醒状态之间的转换。