Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock.
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.
Kim
Do Young
DY
Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, Korea 136-705. yikim@korea.ac.kr
Choi
Hee Joo
HJ
Kim
Jeong Sook
JS
Kim
Yoon Sik
YS
Jeong
Do Ung
DU
Shin
Hyung Cheul
HC
Kim
Mi Jin
MJ
Han
Hee-Chul
HC
Hong
Seung Kil
SK
Kim
Yang In
YI
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
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004338:Drug Combinations; D018698:Glutamic Acid