• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2001년도 학술 발표회 진행표 및 논문초록
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• pp.55-55
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• 2001

We observed the APD of rat ventricle myocyte and the effects of Lithospermic acid that was separated at Salvia miltiorrhiza having used in Oriental medicine by using classical whole cell patch clamp technique. We classified APD into APD30mV, APD0mV, APD-50mV, APD-60mV by cell membrane potential and the mean of cell resting membrane potential was -69.44${\pm}$1.72 mV.(omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.119-125
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• 2010

We investigated the effects of a hot-water extract of Artemisia iwayomogi, a plant belonging to family Compositae, on cardiac ventricular delayed rectifier $K^+$ current ($I_K$) using the patch clamp technique. The carbohydrate fraction AIP1 dose-dependently increased the heart rate with an apparent $EC_{50}$ value of $56.1{\pm}5.5\;{\mu}g/ml$. Application of AIP1 reduced the action potential duration (APD) in concentration-dependent fashion by activating $I_K$ without significantly altering the resting membrane potential ($IC_{50}$ value of $APD_{50}$: $54.80{\pm}2.24$, $IC_{50}$ value of $APD_{90}$: $57.45{\pm}3.47\;{\mu}g/ml$). Based on the results, all experiments were performed with $50\;{\mu}g/ml$ of AIP1. Pre-treatment with the rapidly activating delayed rectifier $K^+$ current ($I_{Kr}$) inhibitor, E-4031 prolonged APD. However, additional application of AIP1 did not reduce APD. The inhibition of slowly activating delayed rectifier $K^+$ current ($I_{Ks}$) by chromanol 293B did not change the effect of AIP1. AIP1 did not significantly affect coronary arterial tone or ion channels, even at the highest concentration of AIP1. In summary, AIP1 reduces APD by activating $I_{Kr}$ but not $I_{Ks}$. These results suggest that the natural product AIP1 may provide an adjunctive therapy of long QT syndrome.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.119-127
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• 2016

Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of $Ca^{2+}$ channel current ($I_{Ca}$) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated $K^+$ channel currents ($I_{Kr}$, $I_{Ks}$) and voltage-gated $Na^+$ channel current ($I_{Na}$). The concentration-dependent inhibition of $Ca^{2+}$ channel currents ($I_{Ca}$) was examined in rat cardiomyocytes; these CCBs have similar potency on $I_{Ca}$ channel blocking with $IC_{50}$ (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both $APD_{50}$ and $APD_{90}$ already at $1{\mu}M$ whereas NIC and AML shortened $APD_{50}$ but not $APD_{90}$ up to $30{\mu}M$. According to ion channel studies, NIC and AML concentration-dependently inhibited $I_{Kr}$ and $I_{Ks}$ while ISR had only partial inhibitory effects (<50% at $30{\mu}M$). Inhibition of $I_{Na}$ was similarly observed in the three CCBs. Since the $I_{Kr}$ and $I_{Ks}$ mainly contribute to cardiac repolarization, their inhibition by NIC and AML could compensate for the AP shortening effects due to the block of $I_{Ca}$.

• The Korean Journal of Physiology
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• 제21권1호
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• pp.1-12
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• 1987

There is evidence that the effect of extracellular $Ca^{2+}$ on heart rate is temperature-dependent: at $38^{\circ}C$ excess $Ca^{2+}$ induces positive chronotropic response, whereas at $30^{\circ}C$ there is no significant chronotropic effect of $Ca^{2+}$. The cause of this temperature-dependency, however, remains still unclear. Therefore, this study was undertaken to investigate the chronotropic effect of external $Ca^{2+}$ at different temperature in the isolated rabbit atria and in the small strips of SA node cut perpendicularly to crista terminalis. In the isolated atria, the $Ca^{2+}$ effect was temperature-dependent: at $35^{\circ}C$ excess $Ca^{2+}$ evoked positive chronotropic response, while at $30^{\circ}C$ there was no significant changes in sinus rate. On the contrary, in the small SA strips external $Ca^{2+}$ induced negative chronotropic effect. At $35^{\circ}C$ changes in $Ca^{2+}$ concentration from 2 to 4, 6, and 10 mM decreased the sinus rate by $2.7{\pm}1.6%$, $11.2{\pm}3.7%$ and $23.2{\pm}8.1%$ respectively. Lowering the temperature to $30^{\circ}C$, the negative chronotropic effect of $Ca^{2+}$ became greater. With intracellular microelectrodes transmembrane potential was recorded in the small SA strips at $30^{\circ}C$, $35^{\circ}C$ and $38^{\circ}C$. As temperature increased from 30 to $38^{\circ}C$, sinus rate was accelerated by $13/min/^{\circ}C$, $APD_{50}$(action ptential duration from peak to 50% repolarization) decreased by $5\;msec/^{\circ}C$, and amplitude of action potential was slightly decreased. With an increase in $Ca^{2+}$ concentrations from 0.5 to 6 mM, overshoot increased and MDP decreased. These $Ca^{2+}$ effects on the overshoot and MDP of action potentials were not altered by temperature. But the $Ca^{2+}$ effects on the rates of diastolic depolarization, systolic depolarization and repolarization were modified by temperature. Discrpancy of the chronotropic effects of $Ca^{2+}$ between isolated atria and small SA strips was discussed.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.386-389
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• 2015

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.