• Journal of Korean Neurosurgical Society
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• v.42 no.3
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• pp.205-210
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• 2007

Objective : Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels mediate the hyperpolarization-activated currents (Ih) that participate in regulating neuronal membrane potential and contribute critically to pacemaker activity, promoting synchronization of neuronal networks. However, distinct regional and cellular localization of HCN channels in the brain have not been precisely defined. Aim of this study was to verify the precise cellular location of HCN1 channels in rat cerebellum to better understand the physiological role these channels play in synaptic transmission between CNS neurons. Methods : HCN1 expression in rat brain was analyzed using immunohistochemistry and electron-microscopic observations. Postsynaptic density-95 (PSD-95), otherwise known as locating and clustering protein, was also examined to clarify its role in the subcellular location of HCN1 channels. In addition, to presume the binding of HCN1 channels with PSD-95, putative binding motifs in these channels were investigated using software-searching method. Results : HCN1 channels were locally distributed at the presynaptic terminal of basket cell and exactly corresponded with the location of PSD-95. Moreover, nine putative SH3 domain of PSD-95 binding motifs were discovered in HCN1 channels from motif analysis. Conclusion : Distinct localization of HCN1 channels in rat cerebellum is possible, especially when analyzed in conjunction with the SH3 domain of PSD-95. Considering that HCN1 channels contribute to spontaneous rhythmic action potentials, it is suggested that HCN1 channels located at the presynaptic terminal of neurons may play an important role in synaptic plasticity.

• 대한약리학회:학술대회논문집
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• 2006.10a
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• pp.84.1-84.1
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• 2006

• BMB Reports
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• v.45 no.11
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• pp.635-640
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• 2012

To understand the effects of HCN as potential mediators in the pathogenesis of epilepsy that evoke long-term impaired excitability; the present study was designed to elucidate whether the alterations of HCN expression induced by status epilepticus (SE) is responsible for epileptogenesis. Although HCN1 immunoreactivity was observed in the hippocampus, its immunoreactivities were enhanced at 12 hrs following SE. Although, HCN1 immunoreactivities were reduced in all the hippocampi at 2 weeks, a re-increase in the expression at 2-3 months following SE was observed. In contrast to HCN1, HCN 4 expressions were un-changed, although HCN2 immunoreactive neurons exhibited some changes following SE. Taken together, our findings suggest that altered expressions of HCN1 following SE may be mainly involved in the imbalances of neurotransmissions to hippocampal circuits; thus, it is proposed that HCN1 may play an important role in the epileptogenic period as a compensatory response.

• Animal cells and systems
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• v.11 no.2
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• pp.199-204
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• 2007

HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, whose gene family consists of four subunits (HCN1-4), mediate depolarizing cation currents and contribute to controlling neuronal excitability. In the present study, immunohistochemical and electrophysiological approaches were used to elucidate the role of HCN channels in the cerebellum. Immunohistochemical labeling for HCN1 and HCN2 channels revealed localized expression of both channels at pinceau, the specialized structure of presynaptic axon terminals of basket cells. To determine the functional role of the presynaptic HCN channels, spontaneous inhibitory postsynaptic currents (IPSCs) were recorded from Purkinje cells, the main synaptic targets of basket cells in the cerebellum. While activation of HCN channels by 8-bromo-cAMP increased amplitude of spontaneous IPSCs, blockade of the activated HCN channels by subsequent ZD7288 application reduced the amplitude of spontaneous IPSCs to the level far below the control. Our results imply that modulation of HCN1 and HCN2 channels in presynaptic terminals of basket cells regulates neurotransmitter release, thereby controlling the excitability of Purkinje cells.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.215-223
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• 2017

The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent $K^+$ and $Ca^{2+}$ channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent $K^+$currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent $K^+$ currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker $Cs^+$ (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent $Ca^{2+}$ channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.

• KSII Transactions on Internet and Information Systems (TIIS)
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• v.13 no.1
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• pp.110-132
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• 2019

To ensure reliable and secure communication in heterogeneous cellular network (HCN) with imperfect channel state information (CSI), we proposed a coordinated multipoint (CoMP) transmission scheme based on dual-threshold optimization, in which only base stations (BSs) with good channel conditions are selected for transmission. First, we present a candidate BSs formation policy to increase access efficiency, which provides a candidate region of serving BSs. Then, we design a CoMP networking strategy to select serving BSs from the set of candidate BSs, which degrades the influence of channel estimation errors and guarantees qualities of communication links. Finally, we analyze the performance of the proposed scheme, and present a dual-threshold optimization model to further support the performance. Numerical results are presented to verify our theoretical analysis, which draw a conclusion that the CoMP transmission scheme can ensure reliable and secure communication in dense HCNs with imperfect CSI.