Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock

Authors

  • Do Young Kim,

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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      D. Y. Kim, H. J. Choi, J. S. Kim and Y. S. Kim contributed equally to this work.

  • Hee Joo Choi,

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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      D. Y. Kim, H. J. Choi, J. S. Kim and Y. S. Kim contributed equally to this work.

  • Jeong Sook Kim,

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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      D. Y. Kim, H. J. Choi, J. S. Kim and Y. S. Kim contributed equally to this work.

  • Yoon Sik Kim,

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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    • *

      D. Y. Kim, H. J. Choi, J. S. Kim and Y. S. Kim contributed equally to this work.

  • Do Ung Jeong,

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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  • Hyung Cheul Shin,

    1. Department of Physiology, Hallym University College of Medicine, Chunchon, Korea 200-702
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  • Mi Jin Kim,

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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  • Hee-Chul Han,

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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  • Seung Kil Hong,

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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  • Yang In Kim

    1. Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705
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Dr Y. I. Kim, as above.
E-mail: yikim@korea.ac.kr

Abstract

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 ω-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) ω-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.

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