• International Journal of Oral Biology
• /
• v.43 no.1
• /
• pp.43-51
• /
• 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 Korean Journal of Physiology and Pharmacology
• /
• v.12 no.5
• /
• pp.267-274
• /
• 2008

Since first discovered in chick skeletal muscles, stretch-activated channels (SACs) have been proposed as a probable mechano-transducer of the mechanical stimulus at the cellular level. Channel properties have been studied in both the single-channel and the whole-cell level. There is growing evidence to indicate that major stretch-induced changes in electrical activity are mediated by activation of these channels. We aimed to investigate the mechanism of stretch-induced automaticity by exploiting a recent mathematical model of rat atrial myocytes which had been established to reproduce cellular activities such as the action potential, $Ca^{2+}$ transients, and contractile force. The incorporation of SACs into the mathematical model, based on experimental results, successfully reproduced the repetitive firing of spontaneous action potentials by stretch. The induced automaticity was composed of two phases. The early phase was driven by increased background conductance of voltage-gated $Na^+$ channel, whereas the later phase was driven by the reverse-mode operation of $Na^+/Ca^{2+}$ exchange current secondary to the accumulation of $Na^+$ and $Ca^{2+}$ through SACs. These results of simulation successfully demonstrate how the SACs can induce automaticity in a single atrial myocyte which may act as a focus to initiate and maintain atrial fibrillation in concert with other arrhythmogenic changes in the heart.

• Journal of Life Science
• /
• v.29 no.11
• /
• pp.1235-1240
• /
• 2019

The aim of this study was to clarify histologically the effects of fermented fishmeal on the growth rate of fish. For this purpose, olive flounders were fed on fermented fishmeal at the substitution ratios of 0, 25, 50, 75, and 100%, and the effects on the liver and muscle were examined by microscopy. The olive flounder fed on fermented fishmeal at the 25% substitution ratio had the best hepatic condition, as indicated by the highest hepatosomatic index and the lowest fatty liver level, when compared with fish fed the other substitution ratios. The olive flounder fed on fermented fishmeal at the 25% substitution ratio had good motility, based on the presence of wide myocytes. The high growth rate in the olive flounder fed on fermented fishmeal at the 25% substitution ratio therefore seemed to be related to the health status of the liver and muscles. Higher amounts of the fermented fishmeal (75% and 100% substitution ratios) suppressed the growth rate due to adverse effects on hepatic function and motility of the olive flounder.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1994.04a
• /
• pp.217-217
• /
• 1994

Calcium entry blockers, capable of inhibiting transmembrane influx of extracellular calcium through specific calcium channels, are useful drugs in the treatment of angina pectoris, hypertension, cardiac arrythmia, and various cardiovascular disorders. Compounds having isoquinoline structures have recently been reported to possess calcium antagonistic action. Therefore, in the present study, we have attempted to synthesize some isoquinoline and related compound.; in order to search for potentially effective chemicals acting on cardiovascular system, and evaluated their pharmacological properties focusing on calcium antagonistic actions. Almost all of the compounds so far synthesized, had inhibitory action against phenylephrine or high potassium-induced contraction in vascular smooth muscle with different degrees of potencies depending on their structures, However, some of tetrahydroisoquinoline analogs showed directly inhibit calcium current in isolated rabbit cardiac myocytes examined by patch clamp techniques. The pharmacological properties of these compounds need more intensive investigation as to whether these chemicals may have developed as a new cardiovascular active drugs. Therefore, we are now under investigation of the mechanism of action of these compounds.

• Journal of Chest Surgery
• /
• v.36 no.4
• /
• pp.277-279
• /
• 2003

A 15 year-old boy was referred to us because of mild dyspnea on exertion and incidentally found heart murmur. On echocardiography, a mass involving mainly interventricular septum and causing left ventricular outflow tract obstruction was detected. Cardiac catheterization demonstrated a transaortic pressure gradient of 20 mmHg. Partial excision of the septal mass was performed via aortotomy under cardiopulmonary bypass. The pathologic diagnosis revealed myocardial hamartoma. The lesion was mainly composed of mature, severely hypertrophic myocytes and intervening fibrosis. During the 5 year of follow-up after the surgery, no evidence of arrhythmia or tumor recurrence was documented.

• Proceedings of the Korean Biophysical Society Conference
• /
• 1996.07a
• /
• pp.40-40
• /
• 1996

Abnormally high $Ca^{2+}$ concentrations have been reported in the cardiac myocytes of diabetic mellitus (DM). In order to elucidate the molecular mechanisms of the intracellular $Ca^{2+}$ overload, the activities of $^{45}$ Ca$^{2+}$ uptake and $^{45}$ Ca$^{2+}$ release were measured from the vesicles of junctional SR (Heavy SR, HSR). (omitted)omitted)

• Proceedings of the Korean Biophysical Society Conference
• /
• 2001.06a
• /
• pp.45-45
• /
• 2001

The Na$^{＋}$-K$^{＋}$ pump, a plasma membrane Na$^{＋}$-K$^{＋}$ ATPase is plays a key role in the regulation and maintenance of Na$^{＋}$ and $K^{＋}$ ion concentration gradients across cell membranes. This enzyme pumps three Na$^{＋}$ out of and two $K^{＋}$ into the cell against their electrochemical gradient by utilizing the energy derived from ATP. Therefore, the Na$^{+}$-K$^{+}$ pump generates a net outward electrical current.(omitted)ted)

• Proceedings of the Korean Biophysical Society Conference
• /
• 2001.06a
• /
• pp.57-57
• /
• 2001

Intracellular pH(pH$\sub$i/) is strictly regulated since it is related to various cellular events such as contractility, signal transduction, ion regulation, cell volume, and energy production etc. In physiological conditions, pH$\sub$i/ of arteriolar smooth muscle faced substantial pressure to be changed during the regulation of blood flow. Therefore it is very important to know the regulatory mechanism of pH$\sub$i/.(omitted)

• Proceedings of the Korean Biophysical Society Conference
• /
• 1997.07a
• /
• pp.27-27
• /
• 1997

The effects of $a_1$-adrenoceptor stimulation on intracellular $Ca^{2+}$ ([C $a^{2+}$]$_{i}$ ) transient, contraction, and L-type $Ca^{2＋}$ current ( $I_{Ca,L}$) were studied in single cells isolated from ventricles of guinea pig hearts. Phenylephrine, $\alpha$$_1$-adrenergic agonist, (5$\times$10$^{-5}$ ~10$^{-4}$ M) produced a biphasic pattern of inotropism： transient negative response (decrease in contraction by 23.9$\pm$2.5% of control) followed by a sustained positive response (increase in contraction by 60.0$\pm$3.4%, mean $\pm$ SD, n=12).(omitted)ted)

• Proceedings of the Korean Biophysical Society Conference
• /
• 1997.07a
• /
• pp.31-31
• /
• 1997

Rapidly activating delayed K current (IKr) in cardiac muscles plays an important in repolarization. Expression of HERG cloned by the study on inherited LQT revealed that it encodes a potassium channel with biophysical properties similar to those of IKr in cardiac myocytes： outward currents activating on depolarization with large tail currents on repolarization, implying the inward rectifying property.(omitted)