title: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate firing of globus pallidus neurons in vivo.
abstract: The globus pallidus plays a significant role in motor control under both health and pathological states. Recent studies have revealed that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels occupy a critical position in globus pallidus pacemaking activity. Morphological studies have shown the expression of HCN channels in the globus pallidus. To investigate the in vivo effects of HCN channels in the globus pallidus, extracellular recordings and behavioral tests were performed in the present study. In normal rats, micro-pressure ejection of 0.05mM ZD7288, the selective HCN channel blocker, decreased the frequency of spontaneous firing in 21 out of the 40 pallidal neurons. The average decrease was 50.4±5.4%. Interestingly, in another 18 out of the 40 pallidal neurons, ZD7288 increased the firing rate by 137.1±27.6%. Similar bidirectional modulation on the firing rate was observed by a higher concentration of ZD7288 (0.5mM) as well as another HCN channel blocker, CsCl. Furthermore, activation of HCN channels by 8-Br-cAMP increased the firing rate by 63.0±9.3% in 15 out of the 25 pallidal neurons and decreased the firing rate by 46.9±9.4% in another 8 out of the 25 pallidal neurons. Further experiments revealed that modulation of glutamatergic but not GABAergic transmission may be involved in ZD7288-induced increase in firing rate. Consistent with electrophysiological results, further studies revealed that modulation of HCN channels also had bidirectional effects on behavior. Taken together, the present studies suggest that HCN channels may modulate the activity of pallidal neurons by different pathways in vivo.
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China. Electronic address: chenleiqd@163.com.
authors: Lei
authors: L
authors: Chen
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Rong
authors: R
authors: Xu
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Feng-Jiao
authors: FJ
authors: Sun
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Yan
authors: Y
authors: Xue
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Xiao-Meng
authors: XM
authors: Hao
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Hong-Xia
authors: HX
authors: Liu
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Hua
authors: H
authors: Wang
authors: Department of Neurology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors: Xin-Yi
authors: XY
authors: Chen
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Zi-Ran
authors: ZR
authors: Liu
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Wen-Shuai
authors: WS
authors: Deng
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Xiao-Hua
authors: XH
authors: Han
authors: Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao 266071, China.
authors: Jun-Xia
authors: JX
authors: Xie
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors: Wing-Ho
authors: WH
authors: Yung
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000166:cytology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011187:Posture / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020531:Subthalamic Nucleus / Q000293:injuries; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014851:Wakefulness
chemical_list: D002316:Cardiotonic Agents; D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D011743:Pyrimidines; C082246:ICI D2788; D002586:Cesium; D015124:8-Bromo Cyclic Adenosine Monophosphate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; C028019:cesium chloride; D014633:Valine
keywords: Firing rate; Globus pallidus; HCN channels; Rat; Single unit recording