Cerebral Cortex Advance Access published online on November 13, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp241
The Modulation of Orexin A on HCN Currents of Pyramidal Neurons in Mouse Prelimbic Cortex
1 Department of Physiology, 2 Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, China, 3 Institute of Molecular Medicine, Peking University, Beijing 100871, China
Address correspondence to Zhian Hu, Department of Physiology, Basic Medical College, Third Military Medical University, Chongqing 400038, China. Email: zhianhu{at}yahoo.com.cn.
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.
Key Words: HCN currents • neural excitability • orexin A • prelimbic cortex • pyramidal neurons
Bo Li and Fang Chen have contributed equally to this work.