RRC ID 134
Author Kim DY, Choi HJ, Kim JS, Kim YS, Jeong DU, Shin HC, Kim MJ, Han HC, Hong SK, Kim YI.
Title Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock.
Journal Eur. J. Neurosci.
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.
Volume 21(5)
Pages 1215-22
Published 2005-3
DOI 10.1111/j.1460-9568.2005.03950.x
PMID 15813931
MeSH Analysis of Variance Animals Calcium Channel Blockers / pharmacology Calcium Channels / classification Calcium Channels / drug effects Calcium Channels / physiology* Circadian Rhythm / drug effects* Circadian Rhythm / physiology Dose-Response Relationship, Radiation Drug Combinations Drug Interactions Electric Stimulation / methods Glutamic Acid / pharmacology* In Vitro Techniques Male Membrane Potentials / drug effects Membrane Potentials / physiology Membrane Potentials / radiation effects Neurons / drug effects Neurons / physiology Rats Statistics, Nonparametric Suprachiasmatic Nucleus / cytology Suprachiasmatic Nucleus / drug effects* Suprachiasmatic Nucleus / physiology
IF 2.832
Times Cited 40