• 제목/요약/키워드: L-type $Ca^{2+}$ current

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이노시톨 삼인산 수용체와 미토콘드리아에 의한 심방 근세포 $Ca^{2+}$ 신호전달의 조절 (Regulation of Atrial $Ca^{2+}$ Signaling by Inositol 1,4,5-Trisphosphate Receptor and Mitochondria)

  • 이향진;라스클리만;마틴모라드;우선희
    • 약학회지
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    • 제48권6호
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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.

Cardiac hypertrophy and abnormal $Ca^{2+}$ handling in transgenic mice overexpressing jnnctate

  • Hong, Chang-Soo;Cho, Myeong-Chan;Kwak, Yong-Geun;Chane, Soo-Wan;Kim, Do-Han
    • 한국생물물리학회:학술대회논문집
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    • 한국생물물리학회 2003년도 정기총회 및 학술발표회
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    • pp.52-52
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    • 2003
  • Junctate is a newly identified integral ER/SR membrane $Ca^{2+}$ binding protein, which is an alternative splicing form of the same gene generating aspartyl $\square$-hydroxylase and junctin. To elucidate the functional role of junctate in heart, transgenic (TG) mice overexpressing mouse cardiac junctate-1 under the control of mouse $\square$$^{~}$ myosin heavy chain promoter were generated. Overexpression of junctate in mouse heart resulted in cardiac hypertrophy, increased fibrosis, bradycardia, arrhythmias and impaired contractility. Overexpression of junctate also led to down-regulation of SERCA2, calsequestrin, calreticulin and RyR, but to up-regulation of NCX and PMCA. The SR $Ca^{2+}$ content decreased and the L-type $Ca^{2+}$ current density and the action potential durations increased in TG cardiomyocytes, which could be the cause for the bradycardia in TG heart. The present work has provided an important example of pathogenesis leading to cardiac hypertrophy and arrhythmia, which was caused by impaired $Ca^{2+}$ handling by overexpression of junctate in heart.n heart.

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Isolation and electrical characterization of the rat spinal dorsal horn neurons

  • Han, Seong-Kyu;Lee, Mun-Han;Ryu, Pan-Dong
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1996년도 춘계학술대회
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    • pp.175-175
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    • 1996
  • The spinal dorsal horn is the area where primary afferent fibers terminate and cutaneous sensory information is Processed. A number of putative neurotransmitter substances, including excitatory and inhibitory amino acids and peptides, are present in this region and sites and cellular mechanisms of their actions have been a target of numerous studies. In this study, single neurons were acutely isolated and the properties of whole cell current and responses to excitatory and inhibitory neurotransmitters were studied by the patch clamp method. Young rats (7-14 days) were anesthetized with diethyl-ether, and the lumbar spinal cord was excised and cut transversely at a thickness of 30$\mu\textrm{m}$ by Vibroslicer. The treatment of spinal slices with low concentration of proteases (pronase and thermolysin 0.75 mg/$m\ell$) and mechanical dissociation yielded isolated neurons with near intact morphology. Multipolar, ellipsoidal and bipolar, and pyramidal cells were shown. By applying step voltage pulses to neurons held at -70 mV, two types of inward currents and one outward currents observed. The fast activating and inactivating inward current was the Na$\^$+/ current because of its fast kinetics and blocking by 0.5${\mu}$M TTX, a specific blocker of Na$\^$+/ channel. The second type of inward currents were sustained. Based on their kinetics and current-voltage relations, it was likely that the second type of inward current was the voltage-dependent Ca$\^$2+/ current. In the presence of TTX, the steady-state currents mainly represented outward K$\^$+/ current which looked like the delayed rectifier K$\^$+/ current. In addition, the membrane currents produced by agonist of excitatory amino acid (EAA) receptor and the endogenous transmitter candidate L-glutamate were recorded in isolated whole-cell voltage clamped neurons as well as responses to inhibitory amino acids (${\gamma}$-amino butyric acid, glycine). Drugs were applied by a method that allows complete exchange of the solution within 1 sec; an infinite number of solutions can be applied to a single cell.

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메시형 알루미늄 전극을 이용한 전기응집/부상 공정에서 Kaoline의 탁도 제거 (Turbidity Removal of Kaolin in an Electrocoagulation/Flotation Process Using a Mesh-type Aluminum Electrode)

  • 정창;김동석;박영식
    • 한국환경과학회지
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    • 제26권5호
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    • pp.563-572
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    • 2017
  • The Electrocoagulation-Flotation (ECF) process has great potential in wastewater treatment. ECF technology is effective in the removal of colloidal particles, oil-water emulsion, organic pollutants such as microalgae, and heavy metals. Numerous studies have been conducted on ECF; however, many of them used a conventional plate-type aluminum anode. In this study, we determined the effect of changing operational parameters such as power supply time, applied current, NaCl concentration, and pH on the turbidity removal efficiency of kaoline. We also determined the effects of different electrolyte types (NaCl, $MgSO_4$, $CaCl_2$, $Na_2SO_4$, and tap water), as well as the differences caused by using a plate-type and mesh-type aluminum anode, on the turbidity removal efficiency. The results showed that the optimal values of ECF time, applied current, NaCl concentration, and pH were 5 min, 0.35 A, 0.4 g/L NaCl in distilled water, and pH 7, respectively. The results also revealed that the turbidity removal efficiency of kaoline in different electrolytes decreased in the following sequence, given the same conductivity: tap water > $CaCl_2$ > $MgSO_4$ > NaCl > $Na_2SO_4$. The turbidity removal efficiency of the mesh-type aluminum anode was significantly greater than the plate-type aluminum anode.

유체 압력에 의한 흰쥐 심실근세포 pH의 감소 및 $Na^+-H^+$ 교환체의 활성화 (Decrease of Intracellular pH and Activation of $Na^+-H^+$ Exchanger by Fluid Pressure in Rat Ventricular Myocytes)

  • 김준철;우선희
    • 약학회지
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    • 제55권3호
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    • pp.247-250
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    • 2011
  • An increase in ventricular pressure can alter cardiac excitation and contraction. Recent report has demonstrated that fluid pressure (FP) suppresses L-type $Ca^{2+}$ current with acceleration of the current inactivation in ventricular myocytes. Since the L-type $Ca^{2+}$ channels known to be regulated by intracellular pH ($pH_i$), this study was designed to explore whether pressurized fluid flow affects pHi in isolated rat ventricular myocytes. A flow of pressurized (~16 dyne/$cm^2$) fluid, identical to that bathing the myocytes, was applied onto single myocytes, and intracellular $H^+$ concentration was monitored using confocal $H^+$ imaging. FP significantly decreased $pH_i$ by $0.07{\pm}0.01$ pH units (n=16, P<0.01). Intracellular acidosis enhances the activity of $Na^+-H^+$ exchanger (NHE). Therefore, we examined if the NHE activity is increased by FP using the NHE inhibitor, HOE642. Although HOE642 did not alter $pH_i$ in control conditions, it decreased $pH_i$ in cells pre-exposed to FP, suggesting enhancement of NHE activity by FP. In addition, FP-induced intracellular acidosis was larger in cells pre-treated with HOE642 than in cells under the control conditions. These results suggest that FP induces intracellular acidosis and that NHE may contribute to extrude $H^+$ during the FP-induced acidosis in rat ventricular myocytes.

Involvement of NMDA Receptor and L-type Calcium Channel in the Excitatory Action of Morphine

  • Koo, Bon-Seop;Shin, Hong-Kee;Kang, Suk-Han;Jun, Jong-Hun
    • The Korean Journal of Physiology and Pharmacology
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    • 제6권5호
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    • pp.241-246
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    • 2002
  • We studied the excitatory action of morphine on the responses of dorsal horn neuron to iontophoretic application of excitatory amino acid and C-fiber stimulation by using the in vivo electrophysiological technique in the rat. In 137 of the 232 wide dynamic range (WDR) neurons tested, iontophoretic application of morphine enhanced the WDR neuron responses to N-methyl-D-aspartate (NMDA), kainate, and graded electrical stimulation of C-fibers. Morphine did not have any excitatory effects on the responses of low threshold cells. Morphine-induced excitatory effect at low ejection current was naloxone-reversible and reversed to an inhibitory action at high ejection current. NMDA receptor, calcium channel and intracellular $Ca^{2+}$ antagonists strongly antagonized the morphine-induced excitatory effect. These results suggest that changes in intracellular ionic concentration, especially $Ca^{2+},$ play an important role in the induction of excitatory effect of morphine in the rat dorsal horn neurons.

Regulation of L-type Calcium Channel Current by Somatostatin in Guinea-Pig Gastric Myocytes

  • Kim, Young-Chul;Sim, Jae-Hoon;Lee, Sang-Jin;Kang, Tong-Mook;Kim, Sung-Joon;Kim, Seung-Ryul;Youn, Sei-Jin;Lee, Sang-Jeon;Xu, Wen Xie;So, In-Suk;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • 제9권2호
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    • pp.103-108
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    • 2005
  • To study the direct effect of somatostatin (SS) on calcium channel current ($I_{Ba}$) in guinea-pig gastric myocytes, $I_{Ba}$ was recorded by using whole-cell patch clamp technique in single smooth muscle cells. Nicardipine ($1{\mu}M$), a L-type $Ca^{2+}$ channel blocker, inhibited $I_{Ba}$ by $98{\pm}1.9$% (n=5), however $I_{Ba}$ was decreased in a reversible manner by application of SS. The peak $I_{Ba}$ at 0 mV were decreased to $95{\pm}1.5$, $92{\pm}1.9$, $82{\pm}4.0$, $66{\pm}5.8$, $10{\pm}2.9$% at $10^{-10}$, $10^{-9}$, $10^{-8}$, $10^{-7}$, $10^{-5}$ M of SS, respectively (n=3∼6; $mean{\pm}SEM$). The steady-state activation and inactivation curves of $I_{Ba}$ as a function of membrane potentials were well fitted by a Boltzmann equation. Voltage of half-activation ($V_{0.5}$) was $-12{\pm}0.5$ mV in control and $-11{\pm}1.9$ mV in SS treated groups (respectively, n=5). The same values of half-inactivation were $-35{\pm}1.4$ mV and $-35{\pm}1.9$ mV (respectively, n=5). There was no significant difference in activation and inactivation kinetics of $I_{Ba}$ by SS. Inhibitory effect of SS on $I_{Ba}$ was significantly reduced by either dialysis of intracellular solution with $GDP_{\beta}S$, a non-hydrolysable G protein inhibitor, or pretreatment with pertussis toxin (PTX). SS also decreased contraction of guinea-pig gastric antral smooth muscle. In conclusion, SS decreases voltage-dependent L-type calcium channel current ($VDCC_L$) via PTXsensitive signaling pathways in guinea-pig antral circular myocytes.

The Effect of NO Donor on Contraction, Cytosolic $Ca^{2+}$ Level and Ionic Currents in Guinea-pig Ileal Smooth Muscle

  • Kwon, Seong-Chun;Park, Ki-Young;Ahn, Duck-Sun;Lee, Young-Ho;Kang, Bok-Soon
    • The Korean Journal of Physiology and Pharmacology
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    • 제4권1호
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    • pp.33-40
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    • 2000
  • This study was designed to clarify the mechanism of the inhibitory action of a nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1), on contraction, cytosolic $Ca^{2+}$ level $([Ca^{2+}]_i)$ and ionic currents in guinea-pig ileum. SIN-1 $(0.01{\sim}100\;{\mu}M)$ inhibited 25 mM KCl- or histamine $(10\;{\mu}M)-induced$ contraction in a concentration-dependent manner. SIN-1 reduced both the 25 mM KCl- and the histamine-stimulated increases in muscle tension in parallel with decreased $[Ca^{2+}]_i.$ Using the patch clamp technique with a holding potential of -60 mV, SIN-1 $(10\;{\mu}M)$ decreased peak Ba currents $(I_{Ba})$ by $30.9{\pm}5.4%$ (n=6) when voltage was stepped from -60 mV to +10 mV and this effect was blocked by ODQ $(1\;{\mu}M),$ a soluble guanylyl cyclase inhibitor. Cu/Zn SOD (100 U/ml), the free radical scavenger, had little effect on basal $I_{Ba},$ and SIN-1 $(10\;{\mu}M)$ inhibited peak $I_{Ba}$ by $32.4{\pm}5.8%$ (n=5) in the presence of Cu/Zn SOD. In a cell clamped at a holding-potential of -40 mV, application of $10\;{\mu}M$ histamine induced an inward current. The histamine-induced inward current was markedly and reversibly inhibited by $10\;{\mu}M$ SIN-1, and this effect was abolished by ODQ $(1\;{\mu}M).$ In addition, SIN-1 markedly increased the depolarization-activated outward $K^+$ currents in the all potential ranges. We concluded that SIN-1 inhibits smooth muscle contraction mainly by decreasing $[Ca^{2+}]_i$ resulted from the inhibition of L-type $Ca^{2+}$ channels and the inhibition of nonselective cation currents and/or by the activation of $K^+$ currents via a cGMP-dependent pathway.

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PARTITIONING RATIO OF DEPLETED URANIUM DURING A MELT DECONTAMINATION BY ARC MELTING

  • Min, Byeong-Yeon;Choi, Wang-Kyu;Oh, Won-Zin;Jung, Chong-Hun
    • Nuclear Engineering and Technology
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    • 제40권6호
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    • pp.497-504
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    • 2008
  • In a study of the optimum operational condition for a melting decontamination, the effects of the basicity, slag type and slag composition on the distribution of depleted uranium were investigated for radioactively contaminated metallic wastes of iron-based metals such as stainless steel (SUS 304L) in a direct current graphite arc furnace. Most of the depleted uranium was easily moved into the slag from the radioactive metal waste. The partitioning ratio of the depleted uranium was influenced by the amount of added slag former and the slag basicity. The composition of the slag former used to capture contaminants such as depleted uranium during the melt decontamination process generally consists of silica ($SiO_2$), calcium oxide (CaO) and aluminum oxide ($Al_2O_3$). Furthermore, calcium fluoride ($CaF_2$), magnesium oxide (MgO), and ferric oxide ($Fe_2O_3$) were added to increase the slag fluidity and oxidative potential. The partitioning ratio of the depleted uranium was increased as the amount of slag former was increased. Up to 97% of the depleted uranium was captured between the ingot phase and the slag phase. The partitioning ratio of the uranium was considerably dependent on the basicity and composition of the slag. The optimum condition for the removal of the depleted uranium was a basicity level of about 1.5. The partitioning ratio of uranium was high, exceeding $5.5{\times}10^3$. The slag formers containing calcium fluoride ($CaF_2$) and a high amount of silica proved to be more effective for a melt decontamination of stainless steel wastes contaminated with depleted uranium.

The Role of $K^+$ Channels on Spontaneous Action Potential in Rat Clonal Pituitary $GH_3$ Cell Line

  • Rhim, Hye-Whon;Baek, Hye-Jung;Ho, Won-Kyung;Earm, Yung-E
    • The Korean Journal of Physiology and Pharmacology
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    • 제4권2호
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    • pp.81-90
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    • 2000
  • The types of $K^+$ channel which determine the pattern of spontaneous action potential (SAP) were investigated using whole-cell variation of patch clamp techniques under current- and voltage-clamp recording conditions in rat clonal pituitary $GH_3$ cells. Heterogeneous pattern of SAP activities was changed into more regular mode with elongation of activity duration and afterhyperpolarization by treatment of TEA (10 mM). Under this condition, exposure of the class III antiarrhythmic agent E-4031 $(5\;{\mu}M)$ to $GH_3$ cells hardly affected SAP activities. On the other hand, the main $GH_3$ stimulator thyrotropin-releasing hormone (TRH) still produced its dual effects (transient hyperpolarization and later increase in SAP frequency) in the presence of TEA. However, addition of $BaCl_2$ (2 mM) in the presence of TEA completely blocked SAP repolarization process and produced membrane depolarization in all tested cells. This effect was observed even in TEA-untreated cells and was not mimicked by higher concentration of TEA (30 mM). Also this barium-induced membrane depolarization effect was still observed after L-type $Ca^{2+}$ channel was blocked by nicardipine $(10\;{\mu}M).$ These results suggest that barium-sensitive current is important in SAP repolarization process and barium itself may have some depolarizing effect in $GH_3$ cells.

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