Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock
Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock
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DOI：
10.1111/j.1460-9568.2005.03950.x
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发表时间：
2005-03-01
影响因子：
3.4
通讯作者：
Kim, YI
中科院分区：
文献类型：
--
作者：
Kim, DY;Choi, HJ;Kim, YI
生物钟的重置是一个重要的过程，帮助哺乳动物适应日常的光暗周期。为了了解光重置是否依赖于电压门控钙通道（VGCC），我们研究了VGCC阻断剂对谷氨酸诱导的下丘脑脑片视交叉上核（SCN）神经元昼夜节律放电活动节律相移的影响。首先，我们发现阿米洛利，尼莫地平和ω-芋螺毒素MVIIC（T-，L-和NPQ-型VGCC拮抗剂，分别）的鸡尾酒完全阻断相位延迟和提前，这是，分别诱导谷氨酸盐应用在早期和深夜。接下来，我们发现：（i）阿米洛利和另一种T型VGCC拮抗剂米贝拉地尔完全阻断延迟而不影响进展;（ii）尼莫地平完全阻断进展，而对延迟的影响较小;和（iii）ω-芋螺毒素MVIIC大部分（如果不是完全的话）阻断延迟和进展。随后的全细胞记录显示，T型钙电流的神经元在腹外侧，而不是背内侧，区域的SCN是较大的，在早于深夜，而L型钙电流没有不同，从早到深夜在这两个地区。这些结果表明，VGCC在谷氨酸诱导的相移中起重要作用，T型对相位延迟更重要，L型对相位提前更重要。此外，结果指出的可能性，夜间调制的T-型钙电流retinorecipient神经元有关的差分参与的T-型VGCC相位延迟和进步。
The resetting of the circadian clock based on photic cues delivered by the glutamatergic retinohypothalamic tract is an important process helping mammals to function adaptively to the daily light-dark cycle. To see if the photic resetting relies on voltage-gated Ca2+ channels (VGCCs), we examined the effects of VGCC blockers on the glutamate-induced phase shifts of circadian firing activity rhythms of suprachiasmatic nucleus (SCN) neurons in hypothalamic slices. First, we found that a cocktail of amiloride, nimodipine and omega-conotoxin MVIIC (T-, L- and NPQ-type VGCC antagonists, respectively) completely blocked both phase delays and advances, which were, respectively, induced by glutamate application in early and late night. Next, we discovered that: (i) amiloride and another T-type VGCC antagonist, mibefradil, completely obstructed the delays without affecting the advances; (ii) nimodipine completely blocked the advances while having less impact on delays; and (iii) omega-conotoxin MVIIC blocked largely, if not entirely, both delays and advances. Subsequent whole-cell recordings revealed that T-type Ca2+ currents in neurons in the ventrolateral, not dorsomedial, region of the SCN were larger during early than late night, whereas L-type Ca2+ currents did not differ from early to late night in both regions. These results indicate that VGCCs play important roles in glutamate-induced phase shifts, T-type being more important for phase delays and L-type being so for phase advances. Moreover, the results point to the possibility that a nocturnal modulation of T-type Ca2+ current in retinorecipient neurons is related to the differential involvement of T-type VGCC in phase delays and advances.