• The Korean Journal of Physiology
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• v.23 no.2
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• pp.339-350
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• 1989

Electrophysiological effects of ammonia was studied in the isolated superfused sinus node and atrial muscle cells of the rabbit heart. No significant changes were observed in the overshoot potential (05), maximum diastolic potential (MDP), and action potential amplitude (APA) of the sinus node cells following superfusion with 3.0 mM ammonia, fifty times upper limit of the normal human plasma level. However the action potential duration (APD) of sinus node cells were significantly prolonged after superfusion with 0.6 mM ammonia for 20 min or with 1.2 and 3.0 mM ammonia for 5 minutes. Ammonia in all the concentrations tested decreased the rate of spontaneous firing (RSF) from the sinus node cells. After superfusion of sinus node cells with 0.3 mM ammonia for 20 min, the RSF significantly decreased from 20 min to 25 min after onset of superfusion while a significant decrement in the RSF was observed from 7 min to 30 min following superfusion with 3.0 mM ammonia for S min. On the other hand, the effects of ammonia on the action potential of the rabbit atrial muscle cell were much similar to those on pacemaker cells except that the atrial cell was generally less sensitive to ammonia. The results suggest that ammonia may cause changes in the action potential of the rabbit cardiac cells by the direct action, and that the cardiac effects of ammonia are generally opposite to those of glycine.

• The Korean Journal of Physiology
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• v.21 no.1
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• pp.1-12
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• 1987

There is evidence that the effect of extracellular $Ca^{2+}$ on heart rate is temperature-dependent: at $38^{\circ}C$ excess $Ca^{2+}$ induces positive chronotropic response, whereas at $30^{\circ}C$ there is no significant chronotropic effect of $Ca^{2+}$. The cause of this temperature-dependency, however, remains still unclear. Therefore, this study was undertaken to investigate the chronotropic effect of external $Ca^{2+}$ at different temperature in the isolated rabbit atria and in the small strips of SA node cut perpendicularly to crista terminalis. In the isolated atria, the $Ca^{2+}$ effect was temperature-dependent: at $35^{\circ}C$ excess $Ca^{2+}$ evoked positive chronotropic response, while at $30^{\circ}C$ there was no significant changes in sinus rate. On the contrary, in the small SA strips external $Ca^{2+}$ induced negative chronotropic effect. At $35^{\circ}C$ changes in $Ca^{2+}$ concentration from 2 to 4, 6, and 10 mM decreased the sinus rate by $2.7{\pm}1.6%$, $11.2{\pm}3.7%$ and $23.2{\pm}8.1%$ respectively. Lowering the temperature to $30^{\circ}C$, the negative chronotropic effect of $Ca^{2+}$ became greater. With intracellular microelectrodes transmembrane potential was recorded in the small SA strips at $30^{\circ}C$, $35^{\circ}C$ and $38^{\circ}C$. As temperature increased from 30 to $38^{\circ}C$, sinus rate was accelerated by $13/min/^{\circ}C$, $APD_{50}$(action ptential duration from peak to 50% repolarization) decreased by $5\;msec/^{\circ}C$, and amplitude of action potential was slightly decreased. With an increase in $Ca^{2+}$ concentrations from 0.5 to 6 mM, overshoot increased and MDP decreased. These $Ca^{2+}$ effects on the overshoot and MDP of action potentials were not altered by temperature. But the $Ca^{2+}$ effects on the rates of diastolic depolarization, systolic depolarization and repolarization were modified by temperature. Discrpancy of the chronotropic effects of $Ca^{2+}$ between isolated atria and small SA strips was discussed.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.219-230
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• 1988

The effect of glycine, structurally the most simple amino acid was investigated on the electrophysiological characteristics of the isolated superfused atrial muscle and sinus node cells of the rabbit heart. Superfusion of the sinus node cell with glycine solution (3, 5 and 8 mM) produced concentration-dependent increments of OS (overshoot potential) and MDP (maximum diastolic potential). Generally action potential amplitude increased as a result of greater increment of OS than that of MDP. The changes in action potential of the sinus node cell peaked in $7{\sim}10{\;}minutes$ after onset of superfusioin. On the contrary to the response to intravenously administered glycine, the rate of spontaneous firing of sinus node cell was invariably increased following superfusion with glycine. Action potential duration manifested as $APD_{60}$ (time to 60% repolarization) was significantly shortened by glycine. And the electrophysiological effects of glycine on the atrial muscle cell were similar to that on the sinus node cells. The results of present study suggest that glycine can exert direct effects on the atrial muscle and sinus node cells of the rabbit heart.

• 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.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.386-389
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• 2015

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

• 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.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.57-63
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• 2004

본 연구에서는 3차원 심근조직에서의 회귀성파동에 대한 수치적 해석결과를 제시한다. 심근 조직에서의 회귀성파동은 심실세동(ventricular fibrillation)의 원인으로 지목되고 있으며 심근세포 이온채널 또는 전기전도시스템 등과 같은 여러 가지 요소들이 관련된 복합적 현상으로 생각되고 있다. 지금까지 이에 관한 많은 연구가 전기생리학적 모델을 이용하여 이루어진바 있으며, 주로 동물 심근세포모델에 기반으로 균일한 2차원 또는 3차원 모델에서의 전기전도 현상 해석을 한 바 있다. 그러나 실제 심장조직의 경우, 두께를 가진 3차원적 형상을 지니고 있으며 층을 따라서 전기생리학적으로 상이한 특성을 가진 세포들로 구성된다. 즉 심근은 층을 가로질러 Epi-cardiac, mid-cardiac, endo-cardiac cell들로 구성되며 각기 다른 APD(action potential duration)을 가지고 있다. 따라서 본 연구에서는 이러한 세가지 종류의 인체 심근세포모델을 사용한 3차원 심근조직에서의 활동전위 전도현상에 대한 결과를 제시한다. 이를 위하여 기존의 인체 3가지 종류의 심근세포 모델을 구현하여 그 타당성을 검토한다. 그리고 이를 바탕으로 3차원 조직모델을 구현하는데, simplified bidomain방법을 사용하였다. 3차원 공간상에서 심근세포에 의한 활동전위 전달현상을 해석하기 위하여 유한요소법을 도입한다. 최종적으로는 3가지의 심근세포층을 가진 3차원 심근조직을 구성하고, 여기에 회귀성 파동을 유도한다. 그리고 단일층으로 이루어진 3차원조직에서의 결과와 비교 분석하여 다세포층에 의한 불균일 효과를 분석하였다.

• Korean Journal of Veterinary Research
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• v.27 no.1
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• pp.27-34
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• 1987

To verify the direct effects of the thyroid hormone ($T_3$) on the rabbit heart, $T_3$-Tyrode solution in vitro was perfused on the normal atrial muscles and enzymatically isolated ventricular myocytes of the rabbit. All the experimental procedures were conducted at $35^{\circ}C$ and the same procedures were repeated after Ca. 120 minutes from the beginning of $T_3$-Tyrode perfusion. Compared to the state between the normal Tyrode solution and $T_3$-Tyrode solution, results were observed on the same cells by electrophysiological methods (conventional intracellular recording and whole cell patch clamping) as soon as possible. The results obtained were as follows : 1. Action potential duration (APD) on the left atrial muscle was reduced under the perfusion of $T_3$-Tyrode. 2. Absolute refractory Period was shortened by $T_3$-Tryrode perfusion. (117 msec./114 msec., 90 msec./78 msec.) 3. Maximal Ca currents ($i_{Ca}$) were decreased in single: ventricular myocytes under the $T_3$-Tyrode (2.98 nA) than under the normal Tyrode (6.65 nA) 4. On I-V relation, reversal potential was shifted to lower membrane potential and membrane potential showing maximal $i_{Ca}$was lowered from +10mV to -20mV by $T_3$ effect. 5. Above results were likely to explain that tachycardia in the hyperthyroid state was caused in part by the reduced repolarization phase and the reduced refractory period due to the decrease of the Ca current.