Stretch-activated K<SUP>⁢</SUP> Channels in Rat Atrial Myocytes

Jae Boum Youm 대한생리학회-대한약리학회 2003 The Korean Journal of Physiology & Pharmacology Vol.13 No.4

Mechanical stimuli to the cardiac myocytes initiate many biochemical and physiological events. Stretch-activated cation channels have been suggested to mediate these events. In this study, cell-attached and inside-out excised-patch clamp methods were used to identify stretch-activated cation channels in adult rat atrial myocytes. Channel openings were increased in cell-attached configuration when negative pressure was applied to the pipette, and also in inside-out excised patches by negative pressure. The channel was not permeable to Cl<SUP>⁣</SUP>, Na<SUP>⁢</SUP> and Cs<SUP>⁢</SUP>, but selectively permeable to K<SUP>⁢</SUP>, and the degree of activation was dependent on the magnitude of negative pressure (full activation at <FONT FACE= 바탕 >∼ ⁣50 mmHg). In symmetrical 140 mM KCl, the slope conductance was 51.2⁑3 pS between the potentials of ⁣80 and 0 mV and 55⁑6 pS between 0 and ⁢80 mV (n=5). Glibenclamide (100<FONT FACE= 바탕 >μM) or ATP (2 mM) failed to block the channel openings, indicating that it is not ATP-sensitive K<SUP>⁢</SUP> channel. Arachidonic acid (30<FONT FACE= 바탕 >μM), which has been shown to activate a K<SUP>⁢</SUP> channel cooperatively with membrane stretch, did not affect the channel activity. GdCl<SUB>3</SUB> (100<FONT FACE= 바탕 >μM) also did not alter the activity. These results demonstrate that the mechanical stretch in rat atrial myocytes activates a novel K<SUP>⁢</SUP>-selective cation channel, which is not associated with other K<SUP>⁢</SUP> channels such as ATP-sensitive and arachidonic acid-activated K<SUP>⁢</SUP> channel.

A Computational Model of Cytosolic and Mitochondrial [Ca<SUP>2+</SUP>] in Paced Rat Ventricular Myocytes

Jae Boum Youm,Seong Woo Choi,Chang Han Jang,Hyoung Kyu Kim,Chae Hun Leem,Nari Kim,Jin Han 대한생리학회-대한약리학회 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.5

We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial Ca²⁺ transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1∼3 Hz) made both the diastolic and systolic [Ca²⁺] bigger in mitochondria as well as in cytosol. As L-type Ca²⁺ channel has key influence on the amplitude of Ca²⁺-induced Ca²⁺ release, the relation between stimulus frequency and the amplitude of Ca²⁺ transients was examined under the low density (1/10 of control) of L-type Ca²⁺ channel in model simulation, where the relation was reversed. In experiment, block of Ca²⁺ uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial Ca²⁺ transients, while it failed to affect the cytosolic Ca²⁺ transients. In computer simulation, the amplitude of cytosolic Ca²⁺ transients was not affected by removal of Ca²⁺ uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [Ca²⁺] in cytosol and eventually abolished the Ca²⁺ transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type Ca²⁺ channel to total transsarcolemmal Ca²⁺ flux could determine whether the cytosolic Ca²⁺ transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic Ca²⁺ affects mitochondrial Ca²⁺ in a beat-to-beat manner, however, removal of Ca²⁺ influx mechanism into mitochondria does not affect the amplitude of cytosolic Ca²⁺ transients.

Role of Stretch-Activated Channels in Stretch-Induced Changes of Electrical Activity

Jae Boum Youm,Su-Hyun Jo,Chae Hun Leem,Won-Kyung Ho,Yung E. 대한생리학회-대한약리학회 2004 The Korean Journal of Physiology & Pharmacology Vol.8 No.1

We developed a cardiac cell model to explain the phenomenon of mechano-electric feedback (MEF), based on the experimental data with rat atrial myocytes. It incorporated the activity of ion channels, pumps, exchangers, and changes of intracellular ion concentration. Changes in membrane excitability and Ca<SUP>2⁢</SUP> transients could then be calculated. In the model, the major ion channels responsible for the stretch-induced changes in electrical activity were the stretch-activated channels (SACs). The re</SUP>lationship between the extent of stretch and activation of SACs was formulated based on the experimental findings. Then, the effects of mechanical stretch on the electrical activity were reproduced. The shape of the action potential (AP) was significantly changed by stretch in the model simulation. The duration was decreased at initial fast phase of repolarization (AP duration at 20% repolarization level from 3.7 to 2.5 ms) and increased at late slow phase of repolarization (AP duration at 90% repolarization level from 62 to 178 ms). The resting potential was depolarized from ⁣75 to ⁣61 mV. This mathematical model of SACs may quantitatively predict changes in cardiomyocytes by mechanical stretch.

Modeling of Arrhythmogenic Automaticity Induced by Stretch in Rat Atrial Myocytes

Youm, Jae-Boum,Leem, Chae-Hun,Zhang, Yin Hua,Kim, Na-Ri,Han, Jin,Earm, Yung-E. The Korean Society of Pharmacology 2008 The Korean Journal of Physiology & Pharmacology Vol.12 No.5

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.

Stretch-activated K^(+) Channels in Rat Atrial Myocytes

Youm, Jae Boum The Korean Physiological Society and The Korean So 2003 The Korean Journal of Physiology & Pharmacology Vol.7 No.6

A Computational Model of Cytosolic and Mitochondrial [$Ca^{2+}$] in Paced Rat Ventricular Myocytes

Youm, Jae-Boum,Choi, Seong-Woo,Jang, Chang-Han,Kim, Hyoung-Kyu,Leem, Chae-Hun,Kim, Na-Ri,Han, Jin The Korean Society of Pharmacology 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.4

We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial $Ca^{2+}$ transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1~3 Hz) made both the diastolic and systolic [$Ca^{2+}]$ bigger in mitochondria as well as in cytosol. As L-type $Ca^{2+}$ channel has key influence on the amplitude of $Ca^{2+}$ -induced $Ca^{2+}$ release, the relation between stimulus frequency and the amplitude of $Ca^{2+}$ transients was examined under the low density (1/10 of control) of L-type $Ca^{2+}$ channel in model simulation, where the relation was reversed. In experiment, block of $Ca^{2+}$ uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial $Ca^{2+}$ transients, while it failed to affect the cytosolic $Ca^{2+}$ transients. In computer simulation, the amplitude of cytosolic $Ca^{2+}$ transients was not affected by removal of $Ca^{2+}$ uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [$Ca^{2+}$] in cytosol and eventually abolished the $Ca^{2+}$ transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type $Ca^{2+}$ channel to total transsarcolemmal $Ca^{2+}$ flux could determine whether the cytosolic $Ca^{2+}$ transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic $Ca^{2+}$ affects mitochondrial $Ca^{2+}$ in a beat-to-beat manner, however, removal of $Ca^{2+}$ influx mechanism into mitochondria does not affect the amplitude of cytosolic $Ca^{2+}$ transients.

미세 표면 구조물을 갖는 패드의 제작 및 STI CMP 특성 연구

정석훈,정재우,박기현,서현덕,박재홍,박범영,주석배,최재영,정해도,Jeong, Suk-Hoon,Jung, Jae-Woo,Park, Ki-Hyun,Seo, Heon-Deok,Park, Jae-Hong,Park, Boum-Young,Joo, Suk-Bae,Choi, Jae-Young,Jeong, Hae-Do 한국전기전자재료학회 2008 전기전자재료학회논문지 Vol.21 No.3

Chemical mechanical polishing (CMP) allows the planarization of wafers with two or more materials. There are many elements such as slurry, polishing pad, process parameters and conditioning in CMP process. Especially, polishing pad is considered as one of the most important consumables because this affects its performances such as WIWNU(within wafer non-uniformity) and MRR(material removal rate). In polishing pad, grooves and pores on its surface affect distribution of slurry, flow and profile of MRR on wafer. A subject of this investigation is to apply CMP for planarization of shallow trench isolation structure using microstructure(MS) pad. MS pad is designed to have uniform structure on its surface and manufactured by micro-molding technology. And then STI CMP performances such as pattern selectivity, erosion and comer rounding are evaluated.

O,p'-DDD가 흰쥐의 신장에 미치는 독성에 관한 면역조직화학적 및 초미세형태학적 연구

배재웅,최종범,임성철,김균홍,기근홍,박동수,전호종,박규호 朝鮮大學校 附設 醫學硏究所 1989 The Medical Journal of Chosun University Vol.14 No.2

o,P'-DDD, a derivative of insecticide DDT, which reveals the toxicity and adrenostatic effet by cortisol biosynthesis in the zona fasciculata of adrenal cortex has been used for the treatment of unoperable adrenocortical carcinoma. Adverse effects of o,P'-DDD were usually dose-related and reversible. Most untoward effects include gastrointestinal disturbances, neuromuscular disorders, depression of central nervous system and skin rash but there is a few reports on its nephrotoxicities. o,P'-DDD in corn oil was administered orally to rats for 28 days to investigate its nephrotoxicity by observation of the ultrastructural changes and immunoglobulin deposition in renal glomeuli. The results obtained were as follows. 1. The ultimate destructive target of intracytoplasmic organelle in endothelium and epithelium of renal glomeruli was mitochondria. The severity of the mitochondrial alterations was dependent of the dosages of o,p'-DDD. 2. The characteristic ultrastructural changes in endothelium of glomerular capillary were swelling and detachment from underlying basement membrane. The splitting and complete separations between endothelium and basement membrane were observed in more advanced lesions by the increased dosage of administration of o,p'-DDD and basement membrane in capillary wall of renal glomeruli was irregular and partly thickened. 3. Amorphous double ring formation, electron dense deposits and multiple myelin figures in mitochondria were characteristic ultrastructural findings in the epithelium of glomeruli. 4. Ig G and Ig M depositions were clearly observed in the capillary lumen, subendothelial area and epithelial cells of proximal convoluted tubule. These depositions were more prominent by the increased of o,p'-DDD dosage. From the above results it is suggested that o,P'-DDD exhibits nephrotoxicity by mitochondrial destruction in epithelium and endothelium of glomerular capillary and the severity of mitochondrial alterations was dose dependent of o,p'-DDD.

LNAPL 로 오염된 토양의 정화를 위한 계면활성제 세척법 적용에 있어서 BTEX 및 계면활성제의 흡착특성 분석

이재원(Jae Won Lee),박준범(Jun Boum Park),박규홍(Kyoo Hong Park) 한국물환경학회 1999 한국물환경학회지 Vol.15 No.4

The sorptive properties of BTEX (Benzene, Toluene, Ethylbenzene, p-Xylene, m-Xylene, o-Xylene) and surfactant onto clay particles were measured in the absence and presence of anionic and nonionic surfactants. The potential effects of nonionic and anionic surfactant sorption onto soil include i) an increase of the fractional organic carbon content in the soil ; ii) a decrease of the transport velocity of surfactant in the subsurface ; and iii) a decrease of the amount of surfactant available in bulk solution for micellar solubilization of hydrophobic organic compounds in soil/aqueous system. Sorption of the surfactant was adequately described by the Langmuir isotherm equations. It was suggested that the surfactants of low concentration might promote the partitioning of sorbed aromatic compounds such as BTEX in polluted soils even when surfactant induced desorption was not initiated. Surfactant/BTEX sorption test and pH test were conducted to optimize treatment conditions applicable to enhanced desorption mechanisms with additives of hydrotrope and Na₃PO₄. As results, Na₃PO₄ effectively reduced sorption of BTEX and surfactant micelle onto clay. When Na₃PO₄ was mixed with surfactants, however, pH was increased to 12 and thus clay particles were become more stable resulting in pore clogging. Anionic surfactant and the additive of SXS (Sodium Xylene Sulfonate) reduced the sorption onto clay particles by the repulsion between the negatively charged soil surface and the negatively ionized surfactant and additive. However, the long-time use of the surfactant and the additives clogged the pores by dispersing clay paricles, and reduced the efficiency of the recovery.

포화지층내 저비중 비수용성 유기용매의 유동제거를 위한 계면활성제법의 조작인자 도출

이재원(Jae Won Lee),박규홍(Kyoo Hong Park),박준범(Jun Boum Park) 大韓環境工學會 1999 대한환경공학회지 Vol.21 No.11