title: Role of HCN channels in neuronal hyperexcitability after subarachnoid hemorrhage in rats.
abstract: Disruption of ionic homeostasis and neuronal hyperexcitability contribute to early brain injury after subarachnoid hemorrhage (SAH). The hyperpolarization-activated/cyclic nucleotide (HCN)-gated channels play critical role in the regulation of neuronal excitability in hippocampus CA1 region and neocortex, in which the abnormal neuronal activities are more readily provoked. This study was to investigate the interactions between HCN channels and hyperneuronal activity after experimental SAH. The present results from whole-cell recordings in rat brain slices indicated that (1) perfusion of hemoglobin (Hb)-containing artificial CSF produced neuronal hyperexcitability and inhibited HCN currents in CA1 pyramidal neurons, (2) nitric oxide/Spermine (NO/Sp), a controlled releaser of nitric oxide, attenuated neuronal excitability and enhanced HCN currents in CA1 pyramidal neurons, while L-nitroarginine (L-NNA), an inhibitor of nitric oxide synthase, reduced the HCN currents; and (3) the inhibitory action of Hb on HCN currents was reversed by application of NO/Sp, which also reduced neuronal hyperexcitability; conversely, L-NNA enhanced inhibitory action of Hb on HCN currents. Additionally, Hb perfusion scavenged the production of nitric oxide and decreased the expression of HCN1 subunits in CA1 region. In the rat SAH model, the expression of HCN1, both at mRNA and protein level, decreased in hippocampus CA1 region at 24 h and more pronounced at 72 h after SAH. These observations demonstrated a reduction of HCN channels expression after SAH and Hb reduced HCN currents in hippocampus CA1 pyramidal neurons. Inhibition of HCN channels by Hb may be a novel pathway for inducing the hyperneuronal excitability after SAH.
authors.affiliation: Department of Neurosurgery, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, Peoples Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Chunxia
authors.initials: C
authors.lastname: Luo
authors.forename: Weihua
authors.initials: W
authors.lastname: Tang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Jiangkai
authors.initials: J
authors.lastname: Lin
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels