NDLI: Orexin A-induced extracellular calcium influx in prefrontal cortex neurons involves L-type calcium channels

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Orexin A-induced extracellular calcium influx in prefrontal cortex neurons involves L-type calcium channels

Content Provider	Springer Nature Link
Author	Xia, J. X. Fan, S. Y. Yan, J. Chen, F. Li, Y. Yu, Z. P. Hu, Z. A.
Copyright Year	2009
Abstract	Orexins, novel excitatory neuropeptides from the lateral hypothalamus, have been strongly implicated in the regulation of sleep and wakefulness. In this study, we explored the effects and mechanisms of orexin A on intracellular free Ca$^{2+}$ concentration ([Ca$^{2+}$]$_{i}$) of freshly dissociated neurons from layers V and VI in prefrontal cortex (PFC). Changes in [Ca$^{2+}$]$_{i}$ were measured with fluo-4/AM using confocal laser scanning microscopy. The results revealed that application of orexin A (0.1 ≈1 μM) induced increase of [Ca$^{2+}$]$_{i}$ in a dose-dependent manner. This elevation of [Ca$^{2+}$]$_{i}$ was completely blocked by pretreatment with selective orexin receptor 1 antagonist SB 334867. While depletion of intracellular Ca$^{2+}$ stores by the endoplasmic reticulum inhibitor thapsigargin (2 μM), [Ca$^{2+}$]$_{i}$ in PFC neurons showed no increase in response to orexin A. Under extracellular Ca$^{2+}$-free condition, orexin A failed to induce any changes of Ca$^{2+}$ fluorescence intensity in these acutely dissociated cells. Our data further demonstrated that the orexin A-induced increase of [Ca$^{2+}$]$_{i}$ was completely abolished by the inhibition of intracellular protein kinase C or phospholipase C activities using specific inhibitors, BIS II (1 μM) and D609 (10 μM), respectively. Selective blockade of L-type Ca$^{2+}$ channels by nifedipine (5 μM) significantly suppressed the elevation of [Ca$^{2+}$]$_{i}$ induced by orexin A. Therefore, these findings suggest that exposure to orexin A could induce increase of [Ca$^{2+}$]$_{i}$ in neurons from deep layers of PFC, which depends on extracellular Ca$^{2+}$ influx via L-type Ca$^{2+}$ channels through activation of intracellular PLC-PKC signaling pathway by binding orexin receptor 1.
Starting Page	125
Ending Page	136
Page Count	12
File Format	PDF
ISSN	11387548
Journal	Journal of Physiology and Biochemistry
Volume Number	65
Issue Number	2
e-ISSN	18778755
Language	Spanish
Publisher	Springer Netherlands
Publisher Date	2009-01-01
Publisher Institution	University of Navarra, Spain
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Sleep/wakefulness Orexin A Prefrontal cortex Protein kinase C Phospholipase C L-type calcium channels Biomedicine general Human Physiology Animal Physiology
Content Type	Text
Resource Type	Article
Subject	Physiology Medicine Biochemistry

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