• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.81-90
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• 2000

The types of $K^+$ channel which determine the pattern of spontaneous action potential (SAP) were investigated using whole-cell variation of patch clamp techniques under current- and voltage-clamp recording conditions in rat clonal pituitary $GH_3$ cells. Heterogeneous pattern of SAP activities was changed into more regular mode with elongation of activity duration and afterhyperpolarization by treatment of TEA (10 mM). Under this condition, exposure of the class III antiarrhythmic agent E-4031 $(5\;{\mu}M)$ to $GH_3$ cells hardly affected SAP activities. On the other hand, the main $GH_3$ stimulator thyrotropin-releasing hormone (TRH) still produced its dual effects (transient hyperpolarization and later increase in SAP frequency) in the presence of TEA. However, addition of $BaCl_2$ (2 mM) in the presence of TEA completely blocked SAP repolarization process and produced membrane depolarization in all tested cells. This effect was observed even in TEA-untreated cells and was not mimicked by higher concentration of TEA (30 mM). Also this barium-induced membrane depolarization effect was still observed after L-type $Ca^{2+}$ channel was blocked by nicardipine $(10\;{\mu}M).$ These results suggest that barium-sensitive current is important in SAP repolarization process and barium itself may have some depolarizing effect in $GH_3$ cells.

• International Journal of Oral Biology
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• v.43 no.1
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• pp.43-51
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• 2018

$K^+$ channels are key components of the primary and secondary basolateral $Cl^-$ pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human $K^+$ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier $K^+$ channel ($I_{Kr}$) in the heart. Mutations in hERG reduce $I_{Kr}$ and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to life-threatening arrhythmias. Paroxetine induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltage-independent during each voltage pulse. In guinea pig ventricular myocytes held at $36^{\circ}C$, treatment with $0.4{\mu}M$ paroxetine for 5 min decreased the action potential duration at 90% of repolarization ($APD_{90}$) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.

• The Transactions of The Korean Institute of Electrical Engineers
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• v.60 no.10
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• pp.1951-1958
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• 2011

The objective of this study is to analyze the performance of digital low-pass differentiators(LPD) and then to provide a method to select effective LPD filter, for detecting spikes of surface motor unit action potentials(MUAP). The successful spike detection of MUAPs is a first important step for EMG signal decomposition. The performances of simple and weighted LPD(SLPD and WLPD) filters are analyzed based on different filter lengths and varying MUAPs from simulated surface EMG signals. The SNR improving coefficient and effective MUAP duration range from the analysis results can be used to select proper LPD filters under the varying conditions of surface EMG.

• Toxicological Research
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• v.24 no.4
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• pp.289-295
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• 2008

Toxicology screening following treatment with astemizole, a histamine receptor antagonist, at oral doses of 0, 10, 30 and 60 mg/kg was carried out in male cynomolgus monkeys (Macaca fascicularis). No dose-related changes in mortality, clinical signs, body weight changes, food consumption, or urine analysis occurred in any animal compared to the vehicle control. However, the high-dose group showed a decrease in BUN and ALP compared to vehicle control group. In addition, the levels of TG, AST, ALP and CK increased. Although astemizole did not produce significant toxicological changes at any dose tested, we predict that it can cause toxicological changes of the liver and heart based on the changes in the serum parameters related to the heart and liver. The Action Potential Duration (APD) was prolonged in the heart of 60 mg/kg treatment group compared to the control group. The APD increase in 60 mg/kg treatment group along the other related changes in toxicological parameters imply that astemizole has major cardiotoxic effects in the cynomolgus monkey. This study is a valuable assessment for predicting the general toxicity and cardiotoxic effects of antihistamine drugs using nonhuman primates.

• The Korean Journal of Physiology
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• v.15 no.2
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• pp.73-81
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• 1981

Experiments were conducted in ischemic decerebrate cats to study the effects of electroacupuncture and electrical stimulation of peripheral nerve on pain reaction. Flexion reflex was used as an index of pain. The reflex was elicited by stimulating the sural nerve(20 V, 0.5 msec duration) and recorded as a compound action potential from the nerve innervated to the semitendinosus muscle. Electroacupuncture was performed, using a 23-gauge hyperdermic needle, on the tsusanli point in the lateral upper tibia of the ipsilateral hindlimb. The common peroneal nerve was selected as a peripheral nerve which may be associated with electroacupuncture action, as it runs through the tissue portion under the tsusanli point. Both for electroacupuncture and the stimulation of common peroneal nerve a stimulus of 20 V-intensity, 2 msec-duration and 2 Hz-frequency was applied for 60 min. The results are summerized as follows: 1) The electroacupuncture markedly depressed the flexion reflex; this effect was eliminated by systemic application of naloxone $(0.02{\sim}0.12\;mg/kg)$, a specific narcotic antagonist. 2) Similarly, the electrical stimulation of the common peroneal nerve significantly depressed the flexion reflex, the effect being reversed by naloxone. 3) When most of the afferent nerves excluding sural nerve in the ipsilateral hindlimb were cut, the effect of electroacupuncture on the flexion reflex was not observed. Whereas direct stimulation of the common peroneal nerve at the proximal end from the cut resulted in a significant reduction of the flexion reflex, again the effect was reversible by naloxone application. 4) Transection of the spinal cord at the thoracic 12 did not eliminate the effect of peripheral nerve stimulation on the flexion reflex and its reversal by naloxone, although the effect was significantly less than that in the animal with spinal cord intact. These results suggest that: 1) the analgesic effect of an electroacupuncture is directly mediated by the nervous system and involves morphine-like substances in CNS, 2) the site of analgesic action of electroacupuncture resides mainly in the brainstem and in part in the spinal cord.

• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.2
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• pp.218-231
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• 1999

Pyramidal cells in the hippocampal CA area were recorded from and filled with neurobiotin in anesthetized rats. The extent of their dendrites and the electropharmacological properties of membrane as well as the effect before and after neurobiotin injection were examined. Pyramidal cells had a high resting membrane potential, a low input resistance, and a large amplitude action potential. A afterhyperpolarization was followed a single action potential. Most pyramidal cells did not display a spontaneous firing. Pyramidal cell displayed weak inward rectification and anodal break excitation in response to negative current injection into the cell. Membrane properties of recorded neurons before and after neurobiotin injection with consecutive current injection were compared. Some properties were significantly increased after labelling(P>0.05); the duration and amplitude of sustained AHP, input resistance, and the number of action potentials for simultaneous intra- and extracellular stimulations. Neurobiotin-filled neurons showed pyramidal morphology. Cells were generally bipolar dendrite processes ramifying in stratum lacunosum-moleculare, radiatum, and oriens.

• Restorative Dentistry and Endodontics
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• v.16 no.2
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• pp.85-98
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• 1991

The aim of this study was to investigate the effect of low - power laser used in the medical field for various purposes to suppress pain responses evoked by noxious electrical or mechanical stimuli. After both inferior alveolar nerves and the left anterior digastric muscle of cats under general anesthesia were exposed, a recording electrode for the jaw opening reflex was inserted into the anterior digastric muscle. The right inferior alveolar nerve was dissected under a surgical microscope until the response of the functional single nerve could be evoked by the electrical stimulation of the dental pulp or oral mucosa. The electrical stimulus was applied with a rectangular pulse of 10 ms duration for measuring the threshold intensity of a single nerve fiber in the inferior alveolar nerve which responds to stimulation of dental pulp and oral mucosa. Then a pulse of 1 ms duration was applied for determination of conduction velocity. A noxious mechanical stimulus to the oral mucosa was applied by clamping the receptive field with an arterial clamp. The Ga-As diodide laser(wave length, 904 nm ; frequency, 1,000 Hz) was irradiated to the prepared tooth cavity, inferior alveolar nerve and oral mucosa as a pulse wave of 2 mW for 6 minutes. This was followed by a continuous wave of 15 mW for 3 minutes. The action potential of the nerve and EMG of the digastric muscle evoked by the noxious electrical stimulus and nerve response to noxious mechanical stimulus were compared at intervals of before, immediately after, and at 5, 10, 20, 40, 60 minutes after laser irradiation. The results were as follows: The conduction velocity of the intrapulpal $A{\delta}$- nerve fiber recorded from the inferior alveolar nerve before irradiation had a mean value of $6.68{\pm}2.07m/sec$. The laser irradiation did not affect the conduction velocity of the AS - nerve fiber and did not change the threshold intensity or amplitude of the action potential either. The EMG of the digastric muscle evoked by noxious electrical stimulation to the tooth was not changed by the laser irradiation, whether in latency, threshold intensity or amplitude. The laser irradiated to the receptive field of the oral mucosa which was subjected to noxious stimuli did not affect the amplitude of the action potential or the frequency either.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.7-15
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• 2004

Nitric oxide (NO) system has been implicated in a wide range of physiological functions in the nervous system. However, the role of NO in regulating the neural activity in the gustatory zone of nucleus tractus solitarius (NTS) has not been established. The present study was aimed to investigate the role of NO in the gustatory NTS neurons. Sprague-Dawley rats, weighing about 50 g, were used. Whole cell patch recording and immunohistochemistry were done to determine the electrophysiological characteristics of the rostral gustatory nucleus of the tractus solitaries and distribution of NO synthases (NOS). Neuronal NOS (nNOS) immunoreactivity was strongly detected along the solitary tract extending from rostral to caudal medulla. Resting membrane potentials of NTS neurons were $-49.2{\pm}2\;mV$ and action potential amplitudes were $68.5{\pm}2\;mV$ with a mean duration measured at half amplitude of $1.7{\pm}0.3\;ms$. Input resistance, determined from the response to a 150 ms, -100 pA hyperpolarizing current pulse, was $385{\pm}15\;M{\Omega}$, Superfusion of SNAP or SNP, NO donors, produced either hyperpolarization (68%), depolarization (5%), or no effect (27%). The hyperpolarization was mostly accompanied by a decrease in input resistance. The hyperpolarization caused by SNAP or SNP increased the time to initiate the first action potential, and decreased the number of action potentials elicited by current injection. SNP or SNAP also markedly decreased the number of firing neural discharges of the spontaneous NTS neural activity under zero current. Superfusion of L-NAME, a NOS inhibitor, slightly depolarized the membrane potential and increased the firing rate of NTS neurons induced by current injection. ODQ, a soluble guanylate cyclase inhibitor, ameliorated the SNAP-induced changes in membrane potential, input resistance and firing rates. 8-Br-cGMP, a non-degradable cell-permeable cGMP, hyperpolarized the membrane potential and decreased the number of action potentials. It is suggested that NO in the gustatory NTS has an inhibitory role on the neural activity of NTS through activating soluble guanylate cyclase.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.99-108
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• 1991

The effect of racemic Ketamine HCl was observed on excitable membranes of sciatic nerve fibres and toe muscles from frog. Ketamine significantly depressed the amplitude of the action potential, maximum rate of rise and that of fall of action potentials of sciatic nerve by dose-dependent and time-course manner, and also it produced the inhibition of $K^+-contracture$ in toe muscle. We used two different ways of sucrose gap method to to obtain the better results from sciatic nerve. We observed and compared the effect of ketamine on sciatic nerve with naloxone, 4-AP (4-aminopyridine) and TEA (Tetraethylammonium). Naloxone significantly but not totally blocked the effect of ketamine both on nerve and on skeletal muscle. 4-AP or TEA by itself had a significant depressant effect on the action potentials on nerve by central perfusion (extracellular perfusion), but both of these drugs did not much affect the action of Ketamine on nerve. The reversibility of effect of Ketamine (10 mM) was observed both on nerve and on skeletal muscles when exposed to drug for short duration. The effects of racemic ketamine described may provide to support that one of the mechanisms of the action of Ketamine on nerve and on muscles of frog might be related to non-specifically effect on receptors within the ion channels $(K^+-channel,\;Na^+-channel\;or\;slow\;Ca^{++}\;channel)$ at higher dose which produces anesthetic effect and also it interacts specifically with one of the opioid receptors or subtype of these receptors which is sensitive to Naloxone at lower dose which produces analgesia.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.46-46
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• 2003

Salviae Miltiorrhizae Radix has been used for treatment of cardiovascular diseases in oriental medicine. To investigate the possible involvement of cardiac ion channel in this effect, we examined electrophysiological effects of the extract of Salviae Miltiorrhizae Radix on action potentials and ionic currents in rat ventricular myocytes. The extracts of Salviae Miltiorrhizae Radix were fractionated into nine fractions, and the effect of each fraction on action potential was tested. The fraction containing monomethyl lithospermic acid-A (LSA-A) induced a significant prolongation of action potential duration (APD). LSA-B which is a major component of Salviae Miltiorrhizae Radix, however, did not cause a significant effect. In voltage clamp experiments, the effects of LSA-A on K currents, Ca currents and Na currents were tested. Neither K currents nor L-type Ca currents were affected by LSA-A. On the contrary, LSA-A significantly slowed down the inactivation kinetics of the Na current with no effect on the fast component of the inactivation process. The amplitude of the peak current and the voltage-dependence of activation were not changed by LSA-A. The effect of LSA-A on Na current was abolished when high concentration of $Ca^{2+}$ buffer (10 mM BAPTA) was included in the pipette solution or when Ca2+ current was blocked by nicardipine (1 $\mu$M) in the bath solution.n.