Hyperpolarization-activated and cyclic nucleotide-gated(HCN) channels,distributing in a variety of tissues,especially in excitable cells such as heart cells and many kinds of neurons,have an important role in the modu...Hyperpolarization-activated and cyclic nucleotide-gated(HCN) channels,distributing in a variety of tissues,especially in excitable cells such as heart cells and many kinds of neurons,have an important role in the modulation of heart rate and neuronal excitability.Different from typical voltage-gated sodium channels and potassium channels,HCN channels were evoked inward currents when the cell was hyperpolarized.More and more recent studies have disclosed that HCN channels play important roles in the nervous system,which were linked with its special electrophysiological features as well as its regulatory effect on the cellular membrane excitability.HCN channels could be modulated by many factors including both extracellular molecules and intracellular signaling cascades,which made its functions complicated in the different condition.Based on its role,HCN channels are presumed to be a promising target for chronic pain and brain disorders.In this paper,we will focus on the advancement of roles of HCN channels in the neural system as well as its complex modulator factors.展开更多
Dysregulation of hyperpolarization-activated cyclic nucleotide-gated cation(HCN)channels alters neuronal excitability.However,the role of HCN channels in status epilepticus is not fully understood.In this study,we est...Dysregulation of hyperpolarization-activated cyclic nucleotide-gated cation(HCN)channels alters neuronal excitability.However,the role of HCN channels in status epilepticus is not fully understood.In this study,we established rat models of pentylenetetrazole-induced status epilepticus.We performed western blot assays and immunofluorescence staining.Our results showed that HCN1 channel protein expression,particularly HCN1 surface protein,was significantly decreased in the hippocampal CA1 region,whereas the expression of HCN2 channel protein was unchanged.Moreover,metabolic glutamate receptor 1(mGluR1)protein expression was increased after status epilepticus.The mGluR1 agonist(RS)-3,5-dihydroxyphenylglycine injected intracerebroventricularly increased the sensitivity and severity of pentylenetetrazole-induced status epilepticus,whereas application of the mGluR1 antagonist(+)-2-methyl-4-carboxyphenylglycine(LY367385)alleviated the severity of pentylenetetrazole-induced status epilepticus.The results from double immunofluorescence labeling revealed that mGluR1 and HCN1 were co-localized in the CA1 region.Subsequently,a protein kinase A inhibitor(H89)administered intraperitoneally successfully reversed HCN1 channel inhibition,thereby suppressing the severity and prolonging the latency of pentylenetetrazole-induced status epilepticus.Furthermore,H89 reduced the level of mGluR1,downregulated cyclic adenosine monophosphate(cAMP)/protein kinase A expression,significantly increased tetratricopeptide repeat-containing Rab8b-interacting protein(TRIP8b)(1a-4)expression,and restored TRIP8b(1b-2)levels.TRIP8b(1a-4)and TRIP8b(1b-2)are subunits of Rab8b interacting protein that regulate HCN1 surface protein.展开更多
It has been suggested that HCN1 is primarily expressed in hippocampus, however little is known about its effects on spatial learning and memory. In the present study, we investigated the effects of non-specific HCN1 b...It has been suggested that HCN1 is primarily expressed in hippocampus, however little is known about its effects on spatial learning and memory. In the present study, we investigated the effects of non-specific HCN1 blocker CsCl on spatial learning and memory by using Morris water maze and in situ hybridization in mice. The results showed CsCl 160 mg/kg ip for 4 days, and the mean escape latency was 34 s longer than that of normal control （P〈0. 01）. In hippocampal tissues, staining for the HCN1 mRNA was stronger in the DG and CA1 region of the hippocampus （P 〈0.05, P〈0.05, when CsCl-administration group was compared with normal group）. Our results suggested that CsCl could significantly affect the spatial learning and memory in mice, and HCN channel is involved in the process of learning and memory.展开更多
基金supported by the Beijing Municipal Natural Science Foundation(7142123)
文摘Hyperpolarization-activated and cyclic nucleotide-gated(HCN) channels,distributing in a variety of tissues,especially in excitable cells such as heart cells and many kinds of neurons,have an important role in the modulation of heart rate and neuronal excitability.Different from typical voltage-gated sodium channels and potassium channels,HCN channels were evoked inward currents when the cell was hyperpolarized.More and more recent studies have disclosed that HCN channels play important roles in the nervous system,which were linked with its special electrophysiological features as well as its regulatory effect on the cellular membrane excitability.HCN channels could be modulated by many factors including both extracellular molecules and intracellular signaling cascades,which made its functions complicated in the different condition.Based on its role,HCN channels are presumed to be a promising target for chronic pain and brain disorders.In this paper,we will focus on the advancement of roles of HCN channels in the neural system as well as its complex modulator factors.
基金supported by the National Natural Science Foundation of China,No.81760242(to MGM).
文摘Dysregulation of hyperpolarization-activated cyclic nucleotide-gated cation(HCN)channels alters neuronal excitability.However,the role of HCN channels in status epilepticus is not fully understood.In this study,we established rat models of pentylenetetrazole-induced status epilepticus.We performed western blot assays and immunofluorescence staining.Our results showed that HCN1 channel protein expression,particularly HCN1 surface protein,was significantly decreased in the hippocampal CA1 region,whereas the expression of HCN2 channel protein was unchanged.Moreover,metabolic glutamate receptor 1(mGluR1)protein expression was increased after status epilepticus.The mGluR1 agonist(RS)-3,5-dihydroxyphenylglycine injected intracerebroventricularly increased the sensitivity and severity of pentylenetetrazole-induced status epilepticus,whereas application of the mGluR1 antagonist(+)-2-methyl-4-carboxyphenylglycine(LY367385)alleviated the severity of pentylenetetrazole-induced status epilepticus.The results from double immunofluorescence labeling revealed that mGluR1 and HCN1 were co-localized in the CA1 region.Subsequently,a protein kinase A inhibitor(H89)administered intraperitoneally successfully reversed HCN1 channel inhibition,thereby suppressing the severity and prolonging the latency of pentylenetetrazole-induced status epilepticus.Furthermore,H89 reduced the level of mGluR1,downregulated cyclic adenosine monophosphate(cAMP)/protein kinase A expression,significantly increased tetratricopeptide repeat-containing Rab8b-interacting protein(TRIP8b)(1a-4)expression,and restored TRIP8b(1b-2)levels.TRIP8b(1a-4)and TRIP8b(1b-2)are subunits of Rab8b interacting protein that regulate HCN1 surface protein.
基金This project was supported by a grant from the NationalNatural Sciences Foundation of China (No .30371639)
文摘It has been suggested that HCN1 is primarily expressed in hippocampus, however little is known about its effects on spatial learning and memory. In the present study, we investigated the effects of non-specific HCN1 blocker CsCl on spatial learning and memory by using Morris water maze and in situ hybridization in mice. The results showed CsCl 160 mg/kg ip for 4 days, and the mean escape latency was 34 s longer than that of normal control （P〈0. 01）. In hippocampal tissues, staining for the HCN1 mRNA was stronger in the DG and CA1 region of the hippocampus （P 〈0.05, P〈0.05, when CsCl-administration group was compared with normal group）. Our results suggested that CsCl could significantly affect the spatial learning and memory in mice, and HCN channel is involved in the process of learning and memory.
