• The Korean Journal of Physiology and Pharmacology
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• 제8권1호
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• pp.33-41
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• 2004

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 $Ca^{2+}$ 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 relationship 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.

• The Korean Journal of Physiology and Pharmacology
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• 제7권6호
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• pp.341-348
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• 2003

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 $Cl^-$, $Na^+$ and $Cs^+$, but selectively permeable to $K^+$, and the degree of activation was dependent on the magnitude of negative pressure (full activation at ${\sim} -50 mmHg). In symmetrical 140 mM KCl, the slope conductance was $51.2{\pm}3$ pS between the potentials of -80 and 0 mV and $55{\pm}6$ pS between 0 and +80 mV (n=5). Glibenclamide ($100{mu}M$) or ATP (2 mM) failed to block the channel openings, indicating that it is not ATP-sensitive $K^+$ channel. Arachidonic acid ($30{mu}M$), which has been shown to activate a $K^+$ channel cooperatively with membrane stretch, did not affect the channel activity. $GdCl_3$ ($100{mu}M$) also did not alter the activity. These results demonstrate that the mechanical stretch in rat atrial myocytes activates a novel $K^+$-selective cation channel, which is not associated with other $K^+$ channels such as ATP-sensitive and arachidonic acid-activated $K^+$ channel.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1998년도 학술발표회
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• pp.39-39
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• 1998

Stretch-activated ion channel that is open by mechanical stress applied on the cell membrane is one of the classes of ion channels. Other than stretch-activated channel itself, it has been also reported that a variety of ion channels could be modulated by a mechanical cell stretch.(omitted)

• 한국동물학회:뉴스레터
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• 제12권2호
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• pp.109.1-109
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• 1995

No Abstract, See Full Text

• 한국동물학회:학술대회논문집
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• 한국동물학회 1995년도 한국생물과학협회 학술발표대회
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• pp.245.1-245
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• 1995

No Abstract, See Full Text

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.1-9
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• 2010

AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.

• 한국수정란이식학회지
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• 제19권2호
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• pp.89-99
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• 2004

음압에 의한 세포막 신전으로 열리는 Stretch-activated channel(SAC)은 세포의 부피조적, 세포의 분화, 혈관 긴장도의 조절, 호르몬 분비 조절에서 SAC 존재 유무를 확인하기 위하여 patch clamp기법을 시행하여 SAC의 조절기전과 전기생리학적인 성질을 조사하였다. 음압이 주어지기 전에는 관찰되지 않던 단일통로 전류가 -20 cm$H_2O$이하의 음압이 주어졌을 때 관찰되었다. 음압에 의해 열리는 단일통로 전류는 $Na^+$이나 $K^+$과 같은 일가 양이온이 존재할 때 관찰되었으나 대신 비투과성인 tetramethylamonium이나 meglumine과 같은 양이온으로 교환해 주면 나타나지 않았다. 이는 이 단일 통로 전류가 양이온만을 투과시키는 nonselective cationic channel(NSC)을 통하여 이동하는 stretch-activated NSC(SA-NSC)임을 시사하였다. 이 SA-NSC 전류는 적혈구나 양서류 난자에서 관찰된 SAC의 전류-전압 관계와 유사한 inward rectification 양상을 나타내었으며 PKA에 의하여 통로활성이 증가하였다. 햄스터 난자에서 관찰되는 SA-NSC는 수정 전부터 2-세포 배아기까지 관찰되었으며 통로전류의 크기는 수정란과 1-세포기 배아에서 가장 크게 관찰되었으며 2-세포기 배아에서는 그 크기가 현저하게 감소하였다. 이와 같이 본 연구에서는 햄스터 난자의 발생 초기 단계에서 전기생리학적 기법을 사용하여 처음으로 SA-NSC존재를 직접 확인하였다. 세포 항상성 유지에 필수적인 이 통로의 일반적인 속성으로 미루어 보아, 햄스터 난자의 수정 전후 난자의 활성과 초기 배아 분화 및 발달에 필수적인 역할을 할 것으로 생각된다.}$1.50개였다. 또한 배란된 성숙난자의 채란 율은 각각 70.2, 74.7 및 54.3%로서 41~50시간째에 회수하였을 때가 가장 낮았다. 두당 회수율에 있어서도 8.25${\pm}$1.34, 8.87${\pm}$1.10 및 5.00${\pm}$1.30개로서 회수시간에 따른 유의적인 차이는 없었다. 회수한 난포내 미성숙 난자의 등급에 있어서 회수시간대별 1등급은 각각 24.2, 19.5 및 12.0%였으며, 2등급의 경우는 41~50시간이 4.0%로서 29~34시간과 35~40시간의 14.4% 및 16.2%보다 유의적(P<0.05)으로 낮았다. 난자의 pH 조절과 용적조절과 같은 생리적 환경 조성에 관여할 것으로 추정된다.았으며, 난포내 난자의 회수율은 투여 호르몬 및 반복사용 여부에 따른 차이는 없었다.떤 특정한 질환의 환자가 상대적으로 많을 가능성이 있으므로 국내에서의 소아 신질환의 발병형태를 보다 체계적으로 조사하고 이를 자료화하기 위해서는 개별 기관들의 연구결과만으로는 미흡하다고 생각되며, 이를 위해서는 전국적인 협동조사가 필요하다고 사료된다.9%$, 좌측 $22.2{\pm}3.9%$, 전체 $44.2{\pm}7.8%$보다 유의하게 감소되었다(p<0.01). 4) 양측성 미만성 결손을 보인 급성 신우신염시 상대적 신섭취율은 우측 $48.9{\pm}1.9%$, 좌측 $51.0{\pm}1.9%$로 대조군의 우측 $49.4{\pm}2.6%$, 좌측 $50.2{\pm}2.5%$에 비해 유의한 차이가 없었으나 절대적 신섭취율은 우측 $18.1{\pm}3.9%$,

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2002년도 제9회 학술 발표회 프로그램과 논문초록
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• pp.35-35
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• 2002

The large conductance $Ca^{2＋}$ -activated $K^{＋}$ channels ($BK_{Ca}$) in vascular smooth muscle have been considered to function as a negative feedback in pressure-induced vasoconstriction. In the present study, the function of cytoskeletons in the regulation of $BK_{Ca}$ and its stretch sensitivity was investigated. Using the inside-out patch clamp technique, we recorded single channel activities of $BK_{Ca}$ with 150 mM KCl in the bath solution (pCa=6.5).(omitted)itted)

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.267-274
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• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제26권2호
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• pp.125-133
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• 2022

Carbon monoxide (CO) is a known gaseous bioactive substance found across a wide array of body systems. The administration of low concentrations of CO has been found to exert an anti-inflammatory, anti-apoptotic, anti-hypertensive, and vaso-dilatory effect. To date, however, it has remained unknown whether CO influences atrial natriuretic peptide (ANP) secretion. This study explores the effect of CO on ANP secretion and its associated signaling pathway using isolated beating rat atria. Atrial perfusate was collected for 10 min for use as a control, after which high atrial stretch was induced by increasing the height of the outflow catheter. Carbon monoxide releasing molecule-2 (CORM-2; 10, 50, 100 μM) and hemin (HO-1 inducer; 0.1, 1, 50 μM), but not CORM-3 (10, 50, 100 μM), decreased high stretch-induced ANP secretion. However, zinc porphyrin (HO-1 inhibitor) did not affect ANP secretion. The order of potency for the suppression of ANP secretion was found to be hemin > CORM-2 >> CORM-3. The suppression of ANP secretion by CORM-2 was attenuated by pretreatment with 5-hydroxydecanoic acid, paxilline, and 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, but not by diltiazem, wortmannin, LY-294002, or NG-nitro-L-arginine methyl ester. Hypoxic conditions attenuated the suppressive effect of CORM-2 on ANP secretion. In sum, these results suggest that CORM-2 suppresses ANP secretion via mitochondrial K_ATP channels and large conductance Ca²⁺-activated K⁺ channels.