title: Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock.
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 Ca(2+) 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 Ca(2+) currents in neurons in the ventrolateral, not dorsomedial, region of the SCN were larger during early than late night, whereas L-type Ca(2+) 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 Ca(2+) current in retinorecipient neurons is related to the differential involvement of T-type VGCC in phase delays and advances.
authors.affiliation: Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705. yikim@korea.ac.kr
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Hee Joo
authors.initials: HJ
authors.lastname: Choi
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Do Ung
authors.initials: DU
authors.lastname: Jeong
authors.forename: Hyung Cheul
authors.initials: HC
authors.lastname: Shin
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hee-Chul
authors.initials: HC
authors.lastname: Han
authors.forename: Seung Kil
authors.initials: SK
authors.lastname: Hong
authors.forename: Yang In
authors.initials: YI
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018709:Statistics, Nonparametric; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004338:Drug Combinations; D018698:Glutamic Acid