The modulation of orexin A on HCN currents of pyramidal neurons in mouse prelimbic cortex.
The hyperpolarization-activated/cyclic nucleotide (HCN)-gated channels make important contributions to neural excitability. In prefrontal cortex, HCN channels are localized on the distal dendrites of layer V pyramidal neurons and decrease neural excitability when they are open. In the present study, using whole-cell voltage clamp recordings, the effect of an arousal peptide, orexin A, on HCN currents in layer V pyramidal neurons from mouse prelimbic cortex (PL), the homolog of the prefrontal cortex was investigated. The results demonstrated that orexin A suppressed HCN currents and shifted their activation curve to a more negative direction. This action of orexin A was blocked by SB334867, an orexin receptor 1 (OXR1) blocker and bisindolylmaleimide, a protein kinase C (PKC) inhibitor, indicating the involvement of OXR1 and PKC. The excitatory effect of orexin A on PL pyramidal neurons was enhanced when HCN currents were diminished, while attenuated when HCN currents were enlarged. In summary, orexin A inhibits HCN currents and enhances excitability of pyramidal neurons in PL, which may contribute to arousal and cognition.
Li
Bo
B
Department of Physiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, China.
Chen
Fang
F
Ye
Jianning
J
Chen
Xiaowei
X
Yan
Jie
J
Li
Yang
Y
Xiong
Ying
Y
Zhou
Zhuan
Z
Xia
Jianxia
J
Hu
Zhian
Z
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001583:Benzoxazoles / Q000494:pharmacology; D001703:Biophysics / Q000379:methods; D002540:Cerebral Cortex / Q000166:cytology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009287:Naphthyridines; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D064446:Orexin Receptors; D000068797:Orexins; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D054815:Cyclic Nucleotide-Gated Cation Channels; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D064446:Orexin Receptors; D000068797:Orexins; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D026941:Sodium Channel Blockers; C082246:ICI D2788; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013779:Tetrodotoxin; D014508:Urea