• The Korean Journal of Physiology
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• v.21 no.2
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• pp.169-177
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• 1987

The effects of higenamine were investigated in the single atrial and ventricular myocyte of the guinea pig by using patch clamp method. The results obtained were as follows: 1) Isoprenaline which is known to be ${\beta}-agonist$ increased the duration of action potential and calcium current in ventricular cells. 2) Higenamine also increased the duration of action potential and calcium current in ventricular myocytes. And its effect was blocked by propranolol. 3) In the atrial cells, isoprenaline showed ${\beta}-agonist$ effects, which were increasing the duration of action potential and calcium current same as in ventricular cells. 4) Higenamine, however, showed the opposite effects of ${\beta}-agonist$ which were decreasing the duration of action potential and calcium current. The above results suggest that higenamine has the typical ${\beta}-agonist$ effect in ventricular cells but inhibitory effect in atrial cells and this effect on atrium could be due to the reduction of calcium current.

• Biomolecules & Therapeutics
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• v.14 no.1
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• pp.19-24
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• 2006

Atrial chambers serve as mechanosensory systems during the haemodynamic or mechanical disturbances, which initiates arrhythmia. Atrial myocytes, lacking t-tubules, have two functionally separate sarcoplasmic reticulums (SRs): those at the periphery close to the surface membrane, and those at the cell interior (center) not associated with the membrane. To explore possible role of fluid pressure (FP) in the regulation of atrial local $Ca^{2+}$ signaling we investigated the effect of FP on subcellular $Ca^{2+}$ signals in isolated rat atrial myocytes using confocal microscopy. FP was applied to whole area of single myocyte with pressurized automatic micro-jet (200-400 $mmH_2O$) positioned close to the cell. Application of FP enhanced spontaneous occurrences of peripheral and central $Ca^{2+}$ sparks with larger effects on the peripheral release sites. Unitary properties of single sparks were not altered by FP. Exposure to higher FP often triggered longitudinal $Ca^{2+}$ wave. These results suggest that fluid pressure may directly alter excitability of atrial myocytes by activating $Ca^{2+}$-dependent ionic conductance in the peripheral membrane and by enhancing spontaneous activation of central myofilaments.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.212-217
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• 2007

In atrial myocytes, lacking t-tubules, $Ca^{2+}$ current ($I_{Ca}$)-initiated $Ca^{2+}$ release at the peripheral junctional sites propagates into the interior of the cell by diffusion of $Ca^{2+}$. We have previously reported that time of activation of the central sites is independent of $I_{Ca}$. In the present study we have probed the effects of Bay K 8644 on $Ca^{2+}$ propagation wave to the center of the myocyte using rapid 2-D confocal $Ca^{2+}$ imaging in the rat atrial myocytes. Enhancement of $I_{Ca}$ by Bay K 8644 accelerated the rate of peripheral $Ca^{2+}$ release, but did not affect the speed of propagation of central release. In contrast, enhancement of $I_{Ca}$ by intracellular cAMP reduced the magnitude of peripheral and central $Ca^{2+}$ transients, but significantly accelerated the speed of central $Ca^{2+}$ release. Our data suggest that the speed of central $Ca^{2+}$ propagation triggered by $I_{Ca}$ is not regulated by the magnitude of either $I_{Ca}$ or local cytosolic $Ca^{2+}$ releases.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.352-357
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• 2004

Atrial myocytes have two functionally separate groups of ryanodine receptors (RyRs): those at the periphery colocalized with L-type $Ca^{2+}$channels (DHPRS) and those a t the cell interior not associated with DHPRs. $Ca^{2+}$ current ($I_{ca}$) directly gates peripheral RyRs on action potential and the subsequent peripheral $Ca^{2+}$ release propagates into the center of atrial myocytes. The mechanisms that regulate the $Ca^{2+}$+ propagation wave remain Poorly understood. Using 2-D confocal$Ca^{2+}$ imaging, we examined the role of inositol 1,4,5-trisphosphate receptor (IP $_3R$) and mitochondria on ($I_{ca}$)- gated local $Ca^{2+}$ signaling in rat atrial myocytes. Blockade of IP $_3R$ by xestospongin C (XeC) partially suppressed the magnitudes of I ca-gated central and peripheral $Ca^{2+}$ releases with no effect on $I_{ca}$. Mitochondrial staining revealed that mitochondria were aligned with ${\thickapprox}2-{\mu}m$ separations in the entire cytoplasm of ventricular and atrial myocytes. Membrane depolarization induced rapid mitochondrial $Ca^{2+}$ rise and decay in the cell periphery with slower rise in the center, suggesting that mitochondria may immediately uptake cytosolic $Ca^{2+}$, released from the peripheral SR on depolarization, and re-release the $Ca^{2+}$ into the cytosol to activate neighboring central RyRs. Our data suggest that the activation of IP $_3R$ and mitochondrial $Ca^{2+}$ handing on action potential may serve as a cofactor for the $Ca^{2+}$ propagation from the DHPR-coupled RyRs to the DHPR-uncoupled RyRs with large gaps between them.

• YAKHAK HOEJI
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• v.59 no.4
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• pp.158-163
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• 2015

Cardiac myocytes are subjected to fluid shear stress during each contraction and relaxation. Under pathological conditions, such as valve disease, heart failure or hypertension, shear stress in cardiac chamber increases due to high blood volume and pressure. The shear stress induces proarrhythmic longitudinal global $Ca^{2+}$ waves in atrial myocytes. In the present study, we further explored underlying cellular mechanism for the shear stress-induced longitudinal global $Ca^{2+}$ wave in isolated rat atrial myocytes. A shear stress of ${\sim}16dyn/cm^2$ was applied onto entire single myocyte using pressurized fluid puffing. Confocal $Ca^{2+}$ imaging was performed to measure local and global $Ca^{2+}$ signals. Shear stress elicited longitudinally propagating global $Ca^{2+}$ wave (${\sim}80{\mu}m/s$). The occurrence of shear stress-induced atrial $Ca^{2+}$ wave was eliminated by the inhibition of ryanodine receptors (RyRs) or inositol 1,4,5-trisphosphate receptors ($IP_3Rs$). In addition, pretreatment of phospholipase C (PLC) inhibitor U73122, but not its inactive analogue U73343, abolished the generation of longitudinal $Ca^{2+}$ wave under shear stress. Our data suggest that shear-induced longitudinal $Ca^{2+}$ wave may be induced by $Ca^{2+}$-induced $Ca^{2+}$ release through the RyRs which is triggered by $PLC-IP_3R$ signaling in atrial myocytes.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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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 Pharmacology
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• v.31 no.3
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• pp.279-284
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• 1995

The aim of the present study was to know whether exogenously administered nitric oxide (NO) may differently modulate muscle mechanics between heart and aorta. We used PIANO method to generate NO. In isolated rat atrial tissues, neither heart rate nor contractility was affected by PIANO $(STZ,\;30{\sim}100\;{\mu}M)$. Only high concentration $(100\;{\mu}M)$ of 8-bromo cyclic GMP slightly depressed cardiac contractility. However, the same concentrations of 8-Br cGMP and PIANO significantly relaxed the rat thoracic aorta contracted with phenylephrine $(0.1\;{\mu}M)$. In isolated rabbit cardiac atrial myocytes, the amplitude of calcium currents were decreased in the whole voltage range by the presence of streptozotocin, which was further potentiated by UV light. Calcium currents were also decreased in those preparations treated with bradykinin, nitroprusside and 8-Br cGMP. These findings suggest that exogenous NO may modulate calcium current in cardiac myocyte. However, it remains why this does not affect myocardial contractility and heart rate. We concluded that NO may differently regulate calcium signal between aorta and heart muscle.

• The Korean Journal of Physiology
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• v.26 no.1
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• pp.27-35
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• 1992

We used the whole cell patch clamp technique to examine the ionic basis for the tail current after depolarizing pulse in single atrial myocytes of the rabbit. We recorded the tail currents during various repolarizations after short depolarizing pulse from a holding potential of -70 mV. The potassium currents were blocked by external 4-aminopyridine and replacement of internal potassium with cesium. The current was reversed to the outward direction above +10 mV. High concentrations of intracellular calcium buffer inhibited the activation of the current. Diltiazem and ryanodine blocked it too. These data suggest that the current is activated by intracellular calcium released from sarcoplasmic reticulumn. When the internal chloride concentration was increased, the inward tail current was increased. The current was partially blocked by the anion transport blocker niflumic acid. The current voltage curve of the niflumic acid sensitive current component shows outward rectification and is well fitted to the current voltage curve of the theoretically predicted chloride current calculated from the constant field equation. The currents recorded in rabbit atrial myocytes, with the method showing isolated outward Na Ca exchange current in ventricular cells of the guinea pig, suggested that chloride conductance could be activated with the activation of Na/ca exchange current. From the above results it is concluded that a chloride sensitive component which is activated by intracellular calcium contributes to tail currents in rabbit atrial cells.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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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 Pharmacology
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• v.32 no.3
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• pp.373-380
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• 1996

Recently we reported that GS 386, 1-(4'-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline, inhibited amplitude of the $Ca^{2+}$ current by reducing the probability of $Ca^{2+}$ channel opening without changing channel kinetics in isolated rabbit atrial myocyte. In the present study, further investigation of the mechanism of action of GS 386 was performed using isolated rat trachealis. GS 386 concentration-dependently relaxed rat trachealis contracted by carbachol $(0.3{\mu}M)$ and high $K^+$(65.4 mM) with $IC_{50}$ 5.24 and 5.67 ${\mu}M$, respectively. Verapamil inhibited more effectively the high $K^+-contracted$ tissues than those with carbachol in the rat trachealis muscle. In $Ca^{2+}-free$ media, $Ca^{2+}-induced$ contraction was inhibited by GS 386. Furthermore, high concentration of GS 386 $(100{\mu}M)$ but not verapamil, attenuated a phasic contraction induced not only by carbachol but also caffeine, indicating that GS386 can enter into the cytoplasm where it may exert secondary actions on internal sites of the muscle, such as sarcoplasmic reticulum. Moreover, GS 386 showed verapamil-resistant component of relaxation and increased cAMP levels in rat trachal smooth muscle. These results suggest that the mechanism of action of GS 386 attributes to not only $Ca^{2+}$ antagonistic action but also weak phosphodiesterase inhibitory action.