• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.37-37
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• 2003

We have shown the $Ca^{2+}$-activated chloride current is present in cardiac myocyte in rabbit pulmonary vein (Kim et al., 2002). This current amplitude was increased as [N $a^{+}$]$_{i}$ was increased and we suggested this chloride current may be involve in the spontaneous action potential frequency change. Since this current is activated by the increase of intracellular $Ca^{2+}$, we would like to test what is the inducer of the increase of [C $a^{2+}$]$_{i}$ between a L-type $Ca^{2+}$-current or a reverse mode of N $a^{+}$-C $a^{2+}$ exchange current. White rabbit (1.5 kg) was used and anesthetized with Ketamin (100 mg/kg). Pulmonary vein (PV) was isolated and sleeve area between left atrium and PV was dissected. Using collagenase (Worthington 0.7 mg/cc), single cardiac myocytes were isolated. In the presence of 15 mM of N $a^{＋}$, three steps of voltage pulses were applied (holding potential : -40 ㎷, -80 ㎷ for 50 msec, 30 ㎷ for 5 msec, 10 ㎷ steps from -70 ㎷ to 60 ㎷). The inward and outward tail current was activated after brief 5 msec prepulse. The outward tail current was blocked by the removal of extracellular chloride substituted by glucuronic acid or by a chloride channel blocker, 5 mM 9-AC. But the inward tail current was still remained even though the amplitude was decreased. The reversal potentials were changed to the direction of the change of chloride equilibrium potential ( $E_{Cl}$ ) but the shift of equilibrium potential was not enough to match to the theoretical equilibrium potential shift. In the presence of L-type $Ca^{2+}$ channel blocker, nifedipine 1 uM, inward tail currents were greatly reduced but the outward current tail currents were still remained. In the presence of N $a^{+}$-C $a^{2+}$ exchange current blocker, 10 uM KB-R7943, the inward and outward tail currents were blocked almost completely. We tried to test the $Ca^{2+}$sensitivity of the chloride current with various [C $a^{2+}$]$_{i}$ in pipette solution from 100 nM to 1 uM but we failed to activate $Ca^{2＋}$-activated chloride currents even though the cell became contracted in the presence of 1 uM $Ca^{2+}$. From these results, we could conclude that the increase of [C $a^{2+}$]$_{i}$ to activate the outward $Ca^{2+}$-activated chloride current was mainly induced by the activation of the reverse mode of N $a^{+}$-C $a^{2+}$ exchanger, But for the increase of [C $a^{2+}$]$_{i}$ to activate the inward tail current, L-type $Ca^{2+}$ current may be the major provoking current. Since the cytosolic increase of [C $a^{2+}$]$_{i}$ through pipette solution have failed to activate $Ca^{2+}$-activated chloride current, this chloride current may have very low $Ca^{2+}$ sensitivity or a comparmental increase $Ca^{2+}$ such as in subsarcolemmal space may activate the chloride current. Since there are several reports and models that the increase of $Ca^{2+}$ in subsarcolemmal space would be over several to tens of uM, both possibility may be valid together.uM, both possibility may be valid together.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.63-74
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• 1995

It has been known that, during hypoxia, the adrenal medulla is activated to release catecholamines (CA) while hypoxia also inhibits high $K^+$ -induced CA secretion in the cultured bovine adrenal chromaffin cells. The present study was attempted to examine the effect of hypoxia on CA secretion evoked by chlinergic stimulation and membrane-depolarization from the isolated perfused rat adrenal glands and also to clarify its mechanism of action. For this purpose, using the isolated rat adrenal glands, the effects of hypoxia on CA release evoked by nicotinic ($N_1$) and muscarinic ($M_1$) receptor agonists, membrane-depolarizing agent, $Ca^{++}$-channel activator, intracellular $Ca^{++}$-releaser and ACh were determined. Experiments were carried out, perfusing Krebs solution pre-equilibrated with a gas mixture of 95% N_2$ and 5% $CO_2$. Hypoxia was maintained for $3{\sim}4$ hours through the experiments. Hypoxia gradually caused a time-dependent seduction in CA secretion evoked by DMPP ($100{\mu}M$), McN-A-343 ($100{\mu}M$), ACh (5.32 mM), Bay-K-8644 ($10{\mu}M$) and high $K^+$ (56 mM) respectively. How-ever, it did not affect CA secretion evoked by cyclopiazonic acid ($10{\mu}M$). Hypoxia itself also did fail to produce any influence on spontaneous secretory response of CA. These experimental results suggest that hypoxia depresses CA release evoked by both cholinergic stimulation and membrane-depolarization from the isolated rat adrenal medulla, and that this inhibitory activity may be due to the result of the direct inhibition of $Ca^{++}$ influx into the chromaffin cells without any effect on the calcium mobilization from the intracellular store.

• Korean Journal of Ichthyology
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• v.23 no.1
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• pp.1-9
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• 2011

Differentially Expressed Gene (DEG) was obtained from Differential Display Reverse Transcription (DDRT)-PCR using Annealing Control Primer (ACP) to search and clone genes related to developmental stages of Sebastes inermis. By using 120 ACPs, the nucleotide sequences obtained from 16 DEGs showing higher expression in 6-month-old skeletal muscle than 18-month-old ones and from 22 DEGs displaying stronger expression in 18-month-old than 6-month-old were analyzed and BLAST was conducted. The results identified that DEGs shared 69~95% homology with genes of parvalbumin (PVALB), nucleoside diphosphate kinase (NDK) B, tropomyosin (TPM), troponin I (TnI), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), muscle-type creatine kinase (CKM2), small EDRK-rich factor 2 (SERF2), adenosine monophosphate deaminase (AMPD), Trimeric intracellular cation channel type A (TRICA), Rho GTPase-activating protein 15 (ARHGAP15), S-formylglutathione hydrolase (Esterase D; ESD), heat shock protein 70 (hsp70), type 1 collagen alpha 2 (COL1A2), glutathione S-transferase, Mid1-interacting protein 1 (Mid1lip1), myosin light chain 1 (MYL1), sarcoplasmic/endoplasmic reticulum calcium ATPase 1B (SERCA1B), and ferritin heavy subunit (FTH1). Expression pattern by developmental stage of DEG14 and PVALB exhibiting strong expression in 6-month-old skeletal muscle was investigated using real time PCR. Expression was reduced as Sebastes inermis grew. Expression of PVALB gene was extremely low after 6 months of age. Expression of CKM2 showed higher expression in 18-month-old skeletal muscle than in 6-month-old muscles, and increased continuously until 4 years old, after which CKM2 expression became gradually reduced. By analysis of tissue-specific expression patterns of DEG, DEG14 was expressed mainly in skeletal muscle, liver, kidney and spleen tissues, whereas PVALB expression was expressed in skeletal muscle and kidney, but not in liver and spleen tissues. CKM2 was expressed in skeletal muscle, kidney, and spleen tissues, but not in liver tissues. PVALB gene was composed of 110 amino acids, which constituted 659 bp nucleotides. The results reported here demonstrate that the expression patterns of parvalbumin and CKM2 could be used as molecular markers for selecting fishes exhibiting fast growth.

• Clinical and Experimental Pediatrics
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• v.51 no.9
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• pp.992-997
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• 2008

Purpose : Hypertension (HTN) is no longer an exclusively adult disease; the prevalence of pediatric HTN is increasing. To understand the evaluation and treatment of childhood HTN in Korea, we investigated, via a questionnaire, how hypertensive children are currently assessed and managed by pediatric cardiologists (CA) and nephrologists (NE). Methods : We surveyed 82 pediatric CA and 77 NE, regarding how they manage hypertensive children in Korea. Results : A total 75 replies were received to our questionnaire request (response rate: 47.15%). Routine blood pressure (BP) checks were more frequently performed by NE (CA: 5.7%, NE: 25%, P=0.03), but most respondents (86%) did not check BP routinely. Mercury sphygmomanometers were the most commonly used devices and ambulatory blood pressure monitoring was not frequently used. The goal BP in treated patients was set at the 95th percentile by 61% of respondents. NE used a lower BP goal in hypertensive children with renal disease (CA: 24%, NE: 64%, P=0.004) or DM (CA: 12.5%, NE: 50%, P=0.003). Angiotensin converting enzyme (ACE) inhibitors were the most commonly used agents (mean: 59%); following ACE inhibitors, CA preferred diuretics for hypertensive children with renal disease or cardiovascular disease, and NE preferred calcium channel blockers, regardless of underlying disease. Self-monitoring was the most frequent method for BP monitoring at home. Conclusion : In Korea, BP measurement is not yet a routine examination in treating hypertension. There are some differences in management strategies vis-$\grave{a}$-vis hypertension, between pediatric cardiologists and nephrologists. For the appropriate management and prevention of secondary disease in long-term studies, standard guidelines and education are needed for pediatricians.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.588-596
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• 2009

Background: To clarify the effect of hypoxia on vascular contractility, we tried to show whether hypoxia induced the release of endothelium-derived relaxing factor (EDRF) and the nature of the underlying mechanism for this release. Material and Method: Isometric contractions were observed in rabbit aorta, and the released EDRF from the rabbit aorta was bioassayed by using rabbit denuded carotid artery. The intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in the cultured rabbit aortic endothelial cells was recorded by a microfluorimeter with using Fura-2/AM. Hypoxia was evoked to the blood vessels or endothelial cells by eliminating the $O_2$ in the aerating gases in the external solution. Chemical hypoxia was evoked by applying deoxyglucose or $CN^-$. Result: Hypoxia relaxed the precontracted rabbit thoracic aorta that had its endothelium, and the magnitude of the relaxation was gradually increased by repetitive bouts of hypoxia. In contrast, hypoxia-induced relaxation was not evoked in the aorta that was denuded of endothelium. In a bioassay experiment, hypoxia released endothelium-derived relaxing factor (EDRF) and the release was inhibited by L-NAME or the $K^+$ channel blocker tetraethylammonium (TEA). In the cultured endothelial cells, hypoxia augmented the ATP-induced increase of the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) and this increase was inhibited by TEA. Furthermore, chemical hypoxia also increased the $Ca^{2+}$ influx. Conclusion: From these results, it can be concluded that hypoxia might induce the release of NO from rabbit aortic endothelial cells by increasing $[[Ca^{2+}]_i$.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.529-541
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• 2003

Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

• Journal of Chest Surgery
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• v.29 no.2
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• pp.199-207
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• 1996

Ischemic myocardial damage is inevitable to cardiac surgery. Myocardial damage after initiation of reperfusion through the coronary arteries is one of the most important determinants of a successful surgery. Adenosine is a potent vasodilator, and is also known to induce rapid cardioplegic arrest by its property of antagonizing cardiac calcium channels and activating the potassium channel. Thus, we initiated this study with adenosine to improve postischemic recovery in the isolated rat heart. We tested the hypothesis that adenosine could be more effective than potassium in inducing rapid cardiac arrest and enhancing postischemlc hemodynamic recovery. Isolated rat hearts, connected to the Langendorff appratus, were perfused with Krebs-Henseleit buffer and all hearts were subjected to arrest for 60 minutes. Three groups of hearts were studied according to the composition of cardioplegic solutions : Group A (n=10), adenosine 10mmo1/L+potassium free modified St. Thomas cardioplegia : Group B (n=10), adenosine 400mo1/L+S1. Thomas cardioplegia:Group C(control, n=10), St. Thomas cardioplegia. Adenosine-treated groups (group A & B) resulted in more rapid cardiac arrest than control group (C) (p< 0.01). There was greater improvement in recovery of coronary blood flow at 20 and 30 minutes of reperfusion in group A and at 20 minutes in group B when compared with control group(p<0.01). Recovery of systolic blood pressure at 10 minutes after reperfusion in group A and B was significantly superior to that in group C (p<0.01). Recovery of dp/dt at 10 minute after reperfusion in group A was also significantly superior to group C (p<0.05). Group A and B showed better recovery rates than control group in aortic blood flow, cardiac output, and heart rate, but there were no statistical differences. CPK levels of coronary flow in group A were significantly low (p< 0.01). We concluded that adenosine-enriched cardioplegic solutions have better effects on rapid cardiac arrest and postischemic recovery when compared with potassium cardioplegia.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.88-95
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• 1996

In an open labeled study, two fixed doses of nimodipine(45mg and 90mg daily) were added to the usual antipsychotic drug treatment (Haloperidol : mean dose=25mg/day) in 20 male chronic schizophrenics for 5 weeks. The purposes of this study were to evaluate the therapeutic effects and the effect an the changes of plasma homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(5-HIAA) levels. The results were as follows : 1) Total BPRS score and thought cluster, paranoid cluster subscores showed linear decreasing trend over the course of the study(P<0.05). Especially the thought cluster and paranoid cluster subscores were significant difference between 45mg and 90mg dose of nimodipine(P<0.05). The improvement rates were 45,45% of 90mg and 11.11% of 45mg, but there was no significant difference between the 45mg and 90mg dose of nimodipine. 2) The scores of extrapyramidal symptoms and adverse events-somatic symptoms showed a linear decreasing trends over the course of study. 3) The changes in the mean plasma HVA and 5-H1AA concentrations by the dosages and durations of combining of nimodipine were not statistically significant. 4) There was no statistical significance in plasma HVA and 5-HIAA of the improved, non-improved goroup. Nimodipine has a possibility os on adjunctive agent for treatment resistant schizophrenics, elderly patients and liable patients for the Side effects to usual antipsychotic drugs. So we suggest that the dosage of nimodipine must be above 90mg/day in the treatment of schizophrenia.

• The Korean Journal of Physiology
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• v.20 no.1
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• pp.17-29
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• 1986

The present study was carried out to observe the effect of triiodothyronine on heart, one of the target organ of thyroid hormone. There are many reports that tachycardia, arrythmia, and agumentation of sodium, potassium pump activity are caused in hyperthyroid animal. To examine these cardiac positive chronotropic effects on sinoatrial (SA) node and atrial muscle, hyperthyroid state was induced experimentally by the injecion of 3,3',5-1-triiodothyronine $(T_3)$ in $3{\sim}6$ month-old rabbits. Then intracellular recordings by inserting glass microelectrode into cell were obtained in SA node and atrial muscle. The results can be summarized as follows : 1) Heartbeat was increased from $169.6{\pm}28.0\;to\;264.2{\pm}18.0$ beats per minute, while body weight was decreased to 68f of the initial body weight (Day 1). 2) In experimental group, the duration of action potential at 80% repolarization was decreased from $148.0{\pm}29.1\;to\;107{\pm}13.6msec$. This suggested the increase heartbeat. 3) The firing rate in hyperthyroid group markedly reduced under the 15 mM potassium Tyrode (p<0.005). 4) In hyperthyroid group, depolarization of atrial muscle cell was lowered significantly in 15 mM (p<0.05), 20 mM (p<0.05) potassium Tyrode solution. 5) Sodium-potassium pump activities in experimental group were higher than those in control group in both SA node (p<0. 1) and atrial muscle (p<0.025). 6) In lower concentration of $MnCl_2$, the excitability of SA node in hyperthyroid group was decreased more than that in control group. Effective inhibitory dose $(ID_{50})$ as 0.6 mM in hyperthyroid statd and 1.1 mM in control group.

• Journal of Chest Surgery
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• v.23 no.3
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• pp.452-464
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• 1990

It is well known that extracellular Calcium plays a very important role in several steps of smooth muscle excitability and contractility, and there have been many concerns about factors influencing the distribution of extracellular Ca++ and the Ca++ flux through the cell membrane of the smooth muscle. Based on the assumption that Mg++ may also play an important role in the excitation and contraction processes of the smooth muscle by taking part in affecting Ca++ distribution and flux, many researches are being performed about the exact role of Mg++, especially in the vascular smooth muscle. But yet the effect of Mg++ in the smooth muscle activity is not clarified, and moreover the mechanism of Mg++ action is almost completely unknown. Present study attempted to clarify the effect of Mg++ on the excitability and contractility in the multiunit and unitary smooth muscle, and the mechanism concerned in it. The preparations used were the guinea-pig aortic strip as the experimental material of the multiunit smooth muscle and the rat uterine strip as the one of the unitary smooth muscle. The tissues were isolated from the sacrificed animal and were prepared for recording the isometric contraction. The effects of Mg++ and Ca++ were examined on the electrically driven or spontaneous contraction of the preparations. And the effects of these ions were also studied on the K+ or norepinephrine contracture. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% 02 and kept at 35oC. The results obtained were as follows: 1] Mg++ suppressed the phasic contraction induced by electrical field stimulation dose-dependently in the guinea-pig aortic strip, while the high concentration of Ca++ never recovered the decreased tension. These phenomena were not changed by the a - or b - adrenergic blocker. 2]Mg++ played the suppressing effect on the low concentration [20 and 40 mM] of K+-contracture in the aortic muscle, but the effect was not shown in the case of 100mM K+-contracture. 3] Mg++ also suppressed the contracture induced by norepinephrine in the aortic preparation. And the effect of Mg++ was most prominent in the contracture by the lowest [10 mM] concentration of norepinephrine. 4] In both the spontaneous and electrically driven contractions of the uterine strip, Mg++ decreased the amplitude of peak tension, and by the high concentration of Ca++ the amplitude of tension was recovered unlike the aortic muscle. 5] The frequency of the uterine spontaneous contraction increased as the [Ca++] / [Mg++] ratio increased up to 2, but the frequency decreased above this level. 6] Mg++ decreased the tension of the low[20 and 40mM] K+-contracture in the uterine smooth muscle, but the effect did not appear in the 100mM K+-contracture. From the above results, the following conclusion could be made. 1] Mg++ seems to suppress the contractility directly by acting on the smooth muscle itself, besides through the indirect action on the nerve terminal, in both the aortic and uterine smooth muscles. 2] The fact that the depressant effect of Mg++ on the K+-contracture is in inverse proportion to an increase of K+ concentration appears resulted from the extent of the opening state of the Ca++ channel. 3] Mg++ may play a depressant role on both the potential dependent and the receptor-operated Ca++ channels. 4] The relationship between the actions of Mg++ and Ca++ seems to be competitive in uterine muscle and non-competitive in aortic strip.