• Title/Summary/Keyword: Late plateau phase

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Effect of Na-Ca Exchange on the Action Potential and the Membrane Current of Rabbit Atrial Cells (단일심근 세포의 활동전압 및 막전류에 대한 Na-Ca 교환기전의 영향)

  • Ho, Won-Kyung;So, In-Suk;Earm, Yung-E
    • The Korean Journal of Physiology
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    • v.23 no.2
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    • pp.313-328
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    • 1989
  • The electrophysiological properties of the inward current contributing to the late plateau phase of the action potential were investigated using the whole cell clamp technique and intracellular dialysis in single atrial cells isolated from the rabbit heart. The inward current was activated by various repolarizing pulses after a brief depolarizing pulse to +40 mV for 2 ms and its time course was similar to that of the late plateau of the action potential. The current was fully activated above the potential of -40 mV and abolished by intracellular EGTA. Ryanodine of $1{\mu}M$ also abolished the late plateau and the inward current. Reduced $Na_o\;to\;30%\;and\;20\;mM\;Na_1$ diminished the late plateau together with the inward current. Diltiazem blocked the activation of the current and Ni in the concentration of $40{\sim}200\;{\mu}M$ decreased the development of the late plateau and the inward current. Fully activated current-voltage relation of the inward current showed exponential voltage dependency which was steeper in more hyperplarizing range. The above findings suggest that the inward current was activated by intracellular calcium and contribute the late plateau phase of the action potential. It could be concluded that the inward current would be the inward component of Na-Ca exchange.

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Sensitivity Analysis of dVm/dtMax_repol to Ion Channel Conductance for Prediction of Torsades de Pointes Risk (다형 심실빈맥의 예측을 위한 dVm/dtMax_repol의 이온채널 전도도에 대한 민감도 분석)

  • Jeong, Da Un;Yoo, Yedam;Marcellinus, Aroli;Lim, Ki Moo
    • Journal of Biomedical Engineering Research
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    • v.43 no.5
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    • pp.331-340
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    • 2022
  • Early afterdepolarization (EAD), a significant cause of fatal ventricular arrhythmias including Torsade de Pointes (TdP) in long QT syndromes, is a depolarizing afterpotential at the plateau or repolarization phase in action potential (AP) profile early before completing one pace. AP duration prolongation is related to EAD but is not necessarily accounted for EAD. Several computational studies suggested EAD can form from an abnormality in the late plateau and/or repolarization phase of AP shape. In this sense, we hypothesized the slope during repolarization has the characteristics to predict TdP risk, mainly focusing on the maximum slope during repolarization (dVm/dtmax_repol). This study aimed to predict the sensitivity of dVm/dtmax_repol to ion channel conductances as a TdP risk metric through a population simulation considering multiple effects of simultaneous reduction in six ion channel conductances of gNaL, gKr, gKs, gto, gK1, and gCaL. Additionally, we verified the availability of dVm/dtmax_repol for TdP risk prediction through the correlation analysis with qNet, the representative TdP metric. We performed the population simulations based on the methodology of Gemmel et al. using the human ventricular myocyte model of Dutta et al. Among the sixion channel conductances, dVm/dtmax_repol and qNet responded most sensitively to the change in gKr, followed by gNaL. Furthermore, dVm/dtmax_repol showed a statistically significant high negative correlation with qNet. The dVm/dtmax_repol values were significantly different according to three TdP risk levels of high, intermediate, and low by qNet (p<0.001). In conclusion, we suggested dVm/dtmax_repol as a new biomarker metric for TdP risk assessment.

Effects of Bay K, cAMP and Isoprenaline on the Na-Ca Exchange Current of Single Rabbit Atrial Cells (토끼 심방근에서 Na-Ca 교환 전류에 대한 Bay K, cAMP, Isoprenaline 효과)

  • Ho, Won-Kyung;Earm, Yung-E
    • The Korean Journal of Physiology
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    • v.24 no.2
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    • pp.377-388
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    • 1990
  • Ca movements during the late plateau phase in rabbit atrium implicate Na-Ca exchange. In single atrial cells isolated from the rabbit the properties of the inward current of Na-Ca exchange were investigated using the whole cell voltage clamp technique. The inward currents were recorded during repolarization following brief 2 ms depolarizing pulse to +40 mV from a holding potential of -70 mV. Followings are the results obtained: 1) When stimulated every 30 sec, the inward currents were activated and reached peak values $6{\sim}12\;ms$ after the beginning of depolarizing pulse. The mean current amplitude was 342 pA/cell. 2) The current decayed spontaneously from the peak activation and the timecourse of the relaxation showed two different phases: fast and slow phase. 3) The recovery of the inward current was tested by paired pulse of various interval. The peak current recovered exponentialy with a time course similar to that of Ca current recovery. 4) Relaxation timecourse was also affected by pulse interval and time constant was reduced almost linearly according to the decrease of pulse interval between 30 sec and 1 sec. 5) The peak inward current was increased by long prepulse stimulation, Bay K, isoprenaline or c-AMP. 6) The relaxation time constant of the inward current was prolonged by Bay K or c-AMP, and shortened by isoprenaline. From the above results, it could be concluded that increase of the calcium current potentiates and prolongs intracellular calcium transients, while shortening of the timecourse by isoprenaline or short interval stimulations might be due to the facilitation of Ca uptake by SR.

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Human Sexuality and Sexual Dysfunction (성(性)생활과 성기능장애)

  • Cho, Doo-Young
    • Korean Journal of Psychosomatic Medicine
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    • v.7 no.1
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    • pp.10-25
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    • 1999
  • Children above age of two are able to have sexual excitement, and they actively seek the pleasure actively or passively through touch and masturbation. In late $60_s$ and early $70_s$, Masters, obstetrician, and Johnson, social worker, illustrated four phases of human sexual responses, namely excitement, plateau, orgasmic and resolution phases in both sexes, and multiple orgasms in the female. Their treatment principles of sexual dysfunctions were largely based on behavioral model, introducing the concepts of sensate focus, dual therapy and sex education. Following Masters and Johnson, Kaplan, psychiatrist and psychoanalyst, in the early and mid-$70_s$ introduced new sex therapy which was based on the combination of analytically-oriented psychotherapy and behavior therapy, and classified sexual dysfunctions into three categories such as desire excitement and orgasmic phase disorders. Since $1980_s$ other medical fields joined the stream, putting the concentrated effort on the treatment of the impotence in the male. They have developed penile prosthesis, local injection therapy, and the administration of oral medications. Nowadays Sildenafil(Viagra) seems the best choice for the treatment of the impotence in the male.

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