• The Korean Journal of Physiology and Pharmacology
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• 제4권2호
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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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• 제43권1호
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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.

• 전기학회논문지
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• 제60권10호
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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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• 제24권4호
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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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• 제15권2호
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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.

• 대한소아치과학회지
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• 제26권2호
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• pp.218-231
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• 1999

마취된 흰쥐를 사용하여 해마의 CA영역에 위치한 피라밋세포들의 세포막 특성을 in vivo의 세포내 기록법에 의해서 관찰한 후 2.5% neurobiotin을 세포내 기록용 미세전극에 채워 세포내로 충진시킨후 충진전과 동일한 실험순서로 반응을 다시 관찰하고 ABC kit를 이용하여 면역조직염색을 행하여 형태학적인 관찰을 하였다. 피라밋세포의 세포내 반응 특성은 높은 휴지막 세포막전위, 낮은 input resistance 그리고 큰 활동전위를 가졌다. neurobiotin 충진 전 후에 따른 세포막 특성의 변화는 sustained AHP의 duration과 amplitude, input resistance, 그리고 세포외 및 세포내 자극에 따른 AP 수에서 유의한 차이를 보였고(P<0.05), 세포외 자극에 의한 억제는 주로 전반부에 나타났으며 CA3 영역에 위치한 이 세포의 형태학적 관찰 결과 세포체는 피라밋층에서 분명한 피라미드 형태를 띄고 있었고 기저 및 선단 가지가 각각 백색판층 및 섬유방-분자층까지 뻗어 있었으며 축삭은 겉질을 향해 기저가지돌기면에서 수직으로 뻗어 있었다. 해마의 주세포인 피라밋세포의 세포막 특성과 세포내 염색지시체(marker)로 주로 쓰이는 neurobiotin에 의해 세포막 특성중 일부가 변화됨을 알 수 있었고, 뇌내의 신경세포연결망이 완전히 보존되어 세포들 사이의 시냅스관계를 추측할 수 있는 in vivo 실험 모델이 응용될 수 있음을 제시하였다.

• Restorative Dentistry and Endodontics
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• 제16권2호
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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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• 제8권1호
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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.

• 대한약리학회지
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• 제27권2호
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• pp.99-108
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• 1991

Racemic ketamine을 사용하여 개구리의 좌골신경 및 toe muscle에 대한 작용을 관찰하였다. 실험방법으로는 214 mM sucrose을 사용하여 서로 다른 두 종류의 투여 방법으로 세포막의 활동 전압에 대한 영향을 electric recording으로 관찰하였다. 즉, intracellular 투여는 single sucrose gap technique으로, extracellar 투여는 double sucrose gap technique을 사용하였으며 그 실험 결과는 아래와 같았다. 1. Racemic ketamine은 개구리의 좌골신경 및 toe muscle의 활동전압을 intracellular 및 extracellular 투여시 모두 의의 있게 억제하였다. 2. 개구의 toe muscle에서 $K^+$-수축을 억제하였다. 3. naloxone은 ketamine의 억제작용을 완전히 차단하지는 못하였다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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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.