• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.4.1-4.13
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• 2018

Two-pore domain $K^+$ (K2P) channels have been shown to modulate neuronal excitability. The physiological role of TWIK-1, the first identified K2P channel, in neuronal cells is largely unknown, and we reported previously that TWIK-1 contributes to the intrinsic excitability of dentate gyrus granule cells (DGGCs) in mice. In the present study, we investigated the coexpression of TWIK-1 and TASK-3, another K2P member, in DGGCs. Immunohistochemical staining data showed that TASK-3 proteins were highly localized in the proximal dendrites and soma of DGGCs, and this localization is similar to the expression pattern of TWIK-1. TWIK-1 was shown to associate with TASK-3 in DGGCs of mouse hippocampus and when both genes were overexpressed in COS-7 cells. shRNA-mediated gene silencing demonstrated that TWIK-1/TASK-3 heterodimeric channels displayed outwardly rectifying currents and contributed to the intrinsic excitability of DGGCs. Neurotensin-neurotensin receptor 1 (NT-NTSR1) signaling triggered the depolarization of DGGCs by inhibiting TWIK-1/TASK-3 heterodimeric channels, causing facilitated excitation of DGGCs. Taken together, our study clearly showed that TWIK-1/TASK-3 heterodimeric channels contribute to the intrinsic excitability of DGGCs and that their activities are regulated by NT-NTSR1 signaling.

• PNF and Movement
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• v.19 no.2
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• pp.195-203
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• 2021

Purpose: Neurodynamic tests are used to examine neural tissue in patients with neuro-musculoskeletal disorders, although this has not yet been established in the intensity of nerve tension application. This study aimed to investigate the acute effects of neural stretching intensity on nerve excitability using the latency and amplitude of nerve conduction velocity test (NCV) analysis. Methods: Thirty young, healthy male and female subjects (mean age = 21.30 years) voluntarily participated in this study. Nerve excitability was assessed using the median sensory NCV test. The latency and amplitude of the NCV test were measured under four different conditions: reference phase (supra-maximal stimulus, without neural stretching), baseline phase (2/3 of the supra-maximal stimulus, without neural stretching), weak stretch phase (2/3 of the supra-maximal stimulus, with weak neural stretching), and strong stretch phase (2/3 of the supra-maximal stimulus, with strong neural stretching). Results: The NCV latency was significantly delayed after one minute of neural stretching at the baseline, weak phase, and strong phase in comparison with the reference phase. The NCV latency was significantly delayed by increasing the strength of neural stretching. Furthermore, the NCV amplitude was significantly increased at the weak and strong phases, which were under neural stretching, in comparison with the baseline phase. The NCV amplitude was significantly increased by increasing the strength of the neural stretching. Conclusion: Transient neural stretching as a neurodynamic test can increase the sensitivity of the nerve without negatively affecting the nervous system. However, based on the results of this study, strong neural stretching in the neurodynamic test may delay the transmission of nerve impulses and hypersensitivity.

• Sleep Medicine and Psychophysiology
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• v.28 no.2
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• pp.53-69
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• 2021

Sleep disorders, increasingly prevalent in the general population, induce impairment in daytime functioning and other clinical problems. As changes in cortical excitability have been reported as potential pathophysiological mechanisms underlying sleep disorders, multiple studies have explored clinical effects of modulating cortical excitability through non-invasive brain stimulation in treating sleep disorders. In this study, we critically reviewed clinical studies using non-invasive brain stimulation, particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), for treatment of sleep disorders. Previous studies have reported inconsistent therapeutic effects of TMS and tDCS for various kinds of sleep disorders. Specifically, low-frequency repetitive TMS (rTMS) and cathodal tDCS, both of which exert an inhibitory effect on cortical excitability, have shown inconsistent therapeutic effects for insomnia. On the other hand, high-frequency rTMS and anodal tDCS, both of which facilitate cortical excitability, have improved the symptoms of hypersomnia. In studies of restless legs syndrome, high-frequency rTMS and anodal tDCS induced inconsistent therapeutic effects. Single TMS and rTMS have shown differential therapeutic effects for obstructive sleep apnea. These inconsistent findings indicate that the distinctive characteristics of each non-invasive brain stimulation method and specific pathophysiological mechanisms underlying particular sleep disorders should be considered in an integrated manner for treatment of various sleep disorders. Future studies are needed to provide optimized TMS and tDCS protocols for each sleep disorder, considering distinctive effects of non-invasive brain stimulation and pathophysiology of each sleep disorder.

• 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 Physiology and Pharmacology
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• v.6 no.6
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• pp.287-291
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• 2002

Intrinsic excitabilities of acutely isolated medial vestibular nucleus (MVN) neurons of rats with normal labyrinth and with undergoing vestibular compensation from 30 min to 24 h after unilateral vestibular deafferentation (UVD) were compared. In control rats, proportions of type A and B cells were 30 and 70%, respectively, however, the proportion of type A cells increased following UVD. Bursting discharge and irregular firing patterns were recorded from 2 to 12 h post UVD. The spontaneous discharge rate of neurons in the ipsilesional MVN increased significantly at 2 h post-UVD and remained high until 12 h post-UVD in both type A and type B cells. After-hyperpolarization (AHP) of the MVN neurons decreased significantly from 2 h post-UVD in both types of cells. These results suggest that the early stage of vestibular compensation after peripheral neurectomy is associated with an increase in intrinsic excitability due to reduction of AHP in MVN neurons.

• Animal cells and systems
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• v.13 no.4
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• pp.357-362
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• 2009

Hesperidin, the most abundant polyphenolic compound found in citrus fruits, has been known to possess neuroprotective, sedative, and anticonvulsive effects on the nervous system. In a recent electrophysiological study, it was reported that hesperidin induced biphasic change in population spike amplitude in hippocampal CA1 neurons in response to both single spike stimuli and theta-burst stimulation depending on its concentration. However, the precise mechanism by which hesperidin acts on neuronal functions has not been fully elucidated. Here, using whole-cell patch-clamp recording, we revealed that hesperidin did not affect excitatory synaptic activities such as basal synaptic transmission and theta-burst LTP. Moreover, in a current injection experiment, spike number, resting membrane potential and action potential threshold also remained unchanged. Taken together, these results indicate that the effects of hesperidin on the neuronal functions such as spiking activity might not be attributable to either modification of excitatory synaptic transmissions or changes in membrane excitability in hippocampal CA1 neuron.

• International Journal of Oral Biology
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• v.42 no.2
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• pp.55-61
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• 2017

Recent studies indicate that mitochondria are an important source of reactive oxygen species (ROS) in the spinal dorsal horn. In our previous study, application of malate, a mitochondrial electron transport complex I substrate, induced a membrane depolarization, which was inhibited by pretreatment with ROS scavengers. In the present study, we used patch clamp recording in the substantia geletinosa (SG) neurons of spinal slices, to investigate the cellular mechanism of mitochondrial ROS on neuronal excitability. DNQX (an AMPA receptor antagonist) and AP5 (an NMDA receptor antagonist) decreased the malate-induced depolarization. In an external calcium free solution and addition of tetrodotoxin (TTX) for blockade of synaptic transmission, the malate-induced depolarization remained unchanged. In the presence of DNQX, AP5 and AP3 (a group I metabotropic glutamate receptor (mGluR) antagonist), glutamate depolarized the membrane potential, which was suppressed by PBN. However, oligomycin (a mitochondrial ATP synthase inhibitor) or PPADS (a P2 receptor inhibitor) did not affect the substrates-induced depolarization. These results suggest that mitochondrial substrate-induced ROS in SG neuron directly acts on the postsynaptic neuron, therefore increasing the ion influx via glutamate receptors.

• Annals of Clinical Neurophysiology
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• v.23 no.2
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• pp.69-81
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• 2021

Cortico-cortical evoked potential (CCEP) mapping is a rapidly developing method for visualizing the brain network and estimating cortical excitability. The CCEP comprises the early N1 component the occurs at 10-30 ms poststimulation, indicating anatomic connectivity, and the late N2 component that appears at < 200 ms poststimulation, suggesting long-lasting effective connectivity. A later component at 200-1,000 ms poststimulation can also appear as a delayed response in some studied areas. Such delayed responses occur in areas with changed excitability, such as an epileptogenic zone. CCEP mapping has been used to examine the brain connections causally in functional systems such as the language, auditory, and visual systems as well as in anatomic regions including the frontoparietal neocortices and hippocampal limbic areas. Task-based CCEPs can be used to measure behavior. In addition to evaluations of the brain connectome, single-pulse electrical stimulation (SPES) can reflect cortical excitability, and so it could be used to predict a seizure onset zone. CCEP brain mapping and SPES investigations could be applied both extraoperatively and intraoperatively. These underused electrophysiologic tools in basic and clinical neuroscience might be powerful methods for providing insight into measures of brain connectivity and dynamics. Analyses of CCEPs might enable us to identify causal relationships between brain areas during cortical processing, and to develop a new paradigm of effective therapeutic neuromodulation in the future.

• Journal of the Korean Academy of Clinical Electrophysiology
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• v.5 no.1
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• pp.73-83
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• 2007

This study aims to examine the effects on nociceptive neuron excitability by application of electroacupuncture in rat with inflammation. It used 20 rats for experiment, divided them into control group, electroacupuncture group (EA group), caused hyperalgesia by injecting ${\lambda}$-carrageenan into hindpaw and conducted treatment three times for experimental period. Change of NFR(reaction time, RMS) showed no significant differences among EA group showed significant differences compared to control group from 48 hours. This study showed that EA group had an effect on nociceptive neurone excitability. Therefore, it is considered that electroacupuncture for pain control will be very desirable.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1463-1467
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• 2003

In the present study, the effects of Ginseng radix and Ophiopogonis tuber on field potentials in rat hippocampal slices and cardiac muscle slices were investigated by multi-channel extracellular recording using MED64 system. The field potentials in the brain slices represent synaptic transmission and nerve excitability, and the field potentials in heart muscles represent muscle contractility. The present results show that the aqueous extract of Ginseng radix enhanced field potentials in the both hippocampal slices and cardiac muscle slices. In contrast, the aqueous extract Ophiopogonis tuber exerted no significant effect on the field potentials in the hippocampal slices and cardiac muscle slices. These results suggest the possibility that Yin-Yang theory could be studied in relation with excitability in neurons and muscles.