• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.24-31
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• 2010

Taurine, 2-aminoethanesulfonic acid, is an abundant free amino acid present in brain cells and exerts many important biological functions such as anti-convulsant, modulation of neuronal excitability, regulation of learning and memory, anti-aggressiveness and anti-alcoholic effects. In the present study, we investigated to explore whether taurine has any protective actions against oxidative stress-induced damages in neuronal cells. ERK I/II regulates signaling pathways involved in nitric oxide (NO) and reactive oxygen species (ROS) production and plays a role in the regulation of cell growth, and apoptosis. We have found that taurine significantly inhibited AMPA induced cortical depolarization in the Grease Gap assays using rat cortical slices. Taurine also inhibited AMPA-induced neuronal cell damage in MTT assays in the differentiated SH-SY5Y cells. When the neuronal cells were treated with $H_2O_2$, levels of NO were increased; however, taurine pretreatment decreased the NO production induced by $H_2O_2$ to approximately normal levels. Interestingly, taurine treatment stimulated ERK I/II activity in the presence of AMPA or $H_2O_2$, suggesting the potential role of ERK I/II in the neuroprotection of taurine. Taken together, taurine has significant neuroprotective actions against AMPA or $H_2O_2$ induced damages in neuronal cells, possibly via activation of ERK I/II.

• International Journal of Oral Biology
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• v.37 no.1
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• pp.17-23
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• 2012

Recent studies indicate that reactive oxygen species (ROS) are critically involved in persistent pain primarily through spinal mechanisms, and that mitochondria are the main source of ROS in the spinal dorsal horn. To investigate whether mitochondrial ROS can induce changes in membrane excitability on spinal substantia gelatonosa (SG) neurons, we examined the effects of mitochondrial electron transport complex (ETC) substrates and inhibitors on the membrane potential of SG neurons in spinal slices. Application of ETC inhibitors, rotenone or antimycin A, resulted in a slowly developing and slight membrane depolarization in SG neurons. Also, application of both malate, a complex I substrate, and succinate, a complex II substrate, caused reversible membrane depolarization and enhanced firing activity. Changes in membrane potential after malate exposure were more prominent than succinate exposure. When slices were pretreated with ROS scavengers such as phenyl-N-tert-buthylnitrone (PBN), catalase and 4- hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), malate-induced depolarization was significantly decreased. Intracellular calcium above $100{\mu}M$ increased malateinduced depolarization, witch was suppressed by cyclosporin A, a mitochondrial permeability transition (MPT) inhibitor. These results suggest that enhanced production of spinal mitochondrial ROS can induce nociception through central sensitization.

• The Korean Journal of Pain
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• v.22 no.1
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• pp.1-15
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• 2009

Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.7
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• pp.3109-3116
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• 2011

We studied the effects of vibration stimulation method on upper limbs spasticity in patients with brain lesion. 21 patients with spasticity of the upper limbs selected and divided randomly 3 groups. And then vibratory stimulation was applied to the triceps brachii muscle in group I(n=7), to biceps brachii muscle in group II (n=7), and to both muscles in group III (n=7). Using Neuro-EMG_Micro to investigate the changes in spinal neuronal excitability, F-waves were measured at before and directly after stimulation, and 10 minutes later and 20 minutes later after stimulation especially. MAS(Modified Ashworth Scale) test for muscle tone and MFT(Manual Function Test) for the upper extremity motor function were performed before stimulation and 20 minutes later after stimulation for the purpose of clinical evaluation. In our study, MAS was significant decreased in all groups, F wave and F/M ratio parameters were decreased in all groups and more decreased specially in group III. MFT was increased in group II and III, and more increased specially in group III. Vibration stimulation reduced the neuronal excitability of spinal cord and also muscle tone, and improved the motor function of the upper extremity. These results suggested that vibration stimulation giving to both muscles(triceps and biceps brachii muscle) at the same time was more efficiency in reducing the neuronal excitability of spinal cord and improving the motor function of the upper limbs.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.135-141
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• 2014

The downregulation of A-type $K^+$ channels ($I_A$ channels) accompanying enhanced somatic excitability can mediate epileptogenic conditions in mammalian central nervous system. As $I_A$ channels are dominantly targeted by dendritic and postsynaptic processings during synaptic plasticity, it is presumable that they may act as cellular linkers between synaptic responses and somatic processings under various excitable conditions. In the present study, we electrophysiologically tested if the downregulation of somatic $I_A$ channels was sensitive to synaptic activities in young hippocampal neurons. In primarily cultured hippocampal neurons (DIV 6~9), the peak of $I_A$ recorded by a whole-cell patch was significantly reduced by high KCl or exogenous glutamate treatment to enhance synaptic activities. However, the pretreatment of MK801 to block synaptic NMDA receptors abolished the glutamate-induced reduction of the $I_A$ peak, indicating the necessity of synaptic activation for the reduction of somatic $I_A$. This was again confirmed by glycine treatment, showing a significant reduction of the somatic $I_A$ peak. Additionally, the gating property of $I_A$ channels was also sensitive to the activation of synaptic NMDA receptors, showing the hyperpolarizing shift in inactivation kinetics. These results suggest that synaptic LTP possibly potentiates somatic excitability via downregulating $I_A$ channels in expression and gating kinetics. The consequential changes of somatic excitability following the activity-dependent modulation of synaptic responses may be a series of processings for neuronal functions to determine outputs in memory mechanisms or pathogenic conditions.

• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.20-21
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• 2002

The inflow of Ca$\^$2＋/ through voltage-activated T-type calcium channels (T-channels) regulates a variety of cellular functions including neuronal excitability, cardiac pacemaker activity, hormone secretion, smooth muscle contraction, and fertilization. Not only are T-channels enormously important for the normal operation of cells, they also playa critical role in pathophysiological conditions such as cardiac hypertrophy and absence epilepsy.(omitted)

• Proceedings of the Korean Biophysical Society Conference
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• 2001.06a
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• pp.53-53
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• 2001

When repolarization of neuronal action potential does not decline monotonically but interrupted by additional depolarization, this prolonged depolarization phase is referred to afterdepolarization(ADP). ADP is considered to playa crucial role in the modulation of neuronal excitability, since it contributes to burst firing. We studied the ionic mechanisms underlying ADP in the soma of dentate granule cells, using rat hippocampal slice (300${\mu}{\textrm}{m}$ in thickness) prepared from 3- to 3-week-old SD rats.(omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.73-77
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• 2003

The effects of nitric oxide on the vestibular function recovery following unilateral labyrinthectomy (UL) were studied. Sprague-Dawley male rats, treated with nitric oxide liberating agent sodium nitroprusside (SNP) and NOS inhibitor $N^G$-nitro-L-arginine methyl ester (L-NAME), were subjected to destruction of the unilateral vestibular apparatus, and then spontaneous nystagmus was observed in the rat. To explore the effects of nitric oxide on the neuronal excitability, whole cell patch clamp technique was applied on isolated medial vestibular nuclear neurons. The frequency of spontaneous nystagmus in SNP treated rats was lesser than that of spontaneous nystagmus in control animals. In contrast, pre-UL treatment with L-NAME resulted in a significant increase in spontaneous nystagmus frequency. In addition, SNP increased the frequency of spontaneous action potential in isolated medial vestibular nuclear neurons. Potassium currents of the vestibular nuclear neurons were inhibited by SNP. After blockade of calcium dependent potassium currents by high EGTA (11 mM) in a pipette solution, SNP did not inhibit outward potassium currents. 1H-[1,2,4] oxadiazolo [4,3-a] quinozalin-1-one (ODQ), a specific inhibitor of soluble guanylyl cyclase, inhibited the effects of SNP on the spontaneous firing and the potassium current. These results suggest that nitric oxide after unilateral labyrinthectomy would help to facilitate vestibular compensation by inhibiting calcium-dependent potassium currents through increasing intracellular cGMP, and consequently would increase excitability in ipsilateral vestibular nuclear neurons.

• 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.10 no.1
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• pp.13-17
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• 2006

Experimentally induced cortical disorganization exhibits many anatomical features which are characteristic of cortical malformations in children with early-onset epilepsy. We used an immunocytochemical technique and extracellular field potential recordings from the dorsal hippocampus to determine whether the excitability of the CA1 pyramidal cells was enhanced in rats with exnerimentallv induced hippocampal dysplasia. Compared with control rats, the MAM-treated rats displayed a decrease of paired pulse inhibition. When $GABA_A$ receptor antagonists were blocked with $10{\mu}M$ bicuculline the amplitude of the second population spike of the MAM-treated of rats was similar to that of the first population spike, as was in the control rats. The MAM-treated rats had fewer somatostatin and parvalbumin-immunoreactive neurons than the control rats. These results suggest that the enhanced neuronal responsiveness of the in vivo recording of the CA1 in this animal model may involve a reduction of CA1 inhibition.