Effects of Adenosine on the Ionic Channel Activated by Metabolic Inhibition in Rabbit Ventricular Myocytes

Han. Jin,Kim. Eui-Yong,Ho. Won-Kyung,Earm. Yung-E 대한생리학회 1996 대한생리학회지 Vol.30 No.1

The objective of the present study was to characterize the role of adenosine in regulation of ATP-sensitive K⁺ channel (K_ATP channel) activity in isolated rabbit ventricular myocytes using the patch clamp technique. Internal adenosine had little effects on KaTr channel activity. In an outside-out patch with intrapipette GTP and ATP, external adenosine stimulated K_ATP channel activity. In an inside-out Patch with intrapipette adenosine, ATP reduced K_ATP channel activity, and GTP stimulated K_ATP channel activity. Adenosine receptor activation shifted the half-maximal inhibition Of K_ATP channel from 70 to 241 μm. These results Suggest that activation of adenosine receptors stimulates K_ATP channels in rabbit ventricular myocytes by reducing the apparent affinity of the channel for ATP. The effect may be important for activating K_ATP channels during early phase of myocardial ischemia.

Effect of Cyclic GMP on the Calcium Current in Rabbit Ventricular Myocytes

Han, Jin,Leem, Chae-Hun,Ahn, Chul-Soo,So, In-Suk,Kim, Eui-Yong,Ho, Won-Kyung,Earm, Yung-E The Korean Physiological Society 1993 대한생리학회지 Vol.27 No.2

In order to investigate the effect of intracellular cyclic GMP on calcium current the whole-cell patch clamp technique with internal perfusion method was used in isolated ventricular myocytes of the rabbit. Cyclic GMP, 8-bromo-cyclic GMP, cyclic AMP, isoprenaline and forskolin were perfused into cells and their effects on calcium current were analysed by applying depolarizing step pulses of + 10 mV in amplitude far 300 msec from holding potential of - 40 mV. Not only cyclic AMP $(100\;{\mu}M)$ but also cyclic GMF $(100\;{\mu}M)$ increased the basal calcium current. 8-Bromo-cyclic GMP $(100\;{\mu}M)$, a good stimulator of the cyclic GMP-dependent protein kinase, also increased the basal calcium current and its peak amplitude of calcium current was larger than that in the presence of cyclic AMP or cyclic GMP alone. In the presence of $100\;{\mu}M$ cyclic GMP or $100\;{\mu}M$ 8-bromo-cyclic GMP, already augmented calcium current was potentiated by intracellular application of $100\;{\mu}M$ cyclic AMP or $1\;{\mu}M$ isoprenaline or $1\;{\mu}M$ forskolin. In the presence of cyclic GMP, acetylcholine reduced the calcium current only when the calcium current was increased by isoprenaline. From the above results it could be concluded that intracellular perfusion with cyclic GMP increases the basal calcium current via a mechanism involving a cyclic GMP-dependent protein kinase.

Thiol-dependent Redox Mechanisms in the Modification of ATP-Sensitive Potassium Channels in Rabbit Ventricular Myocytes

Han, Jin,Kim, Na-Ri,Cuong, Dang-Van,Kim, Chung-Hui,Kim, Eui-Yong The Korean Society of Pharmacology 2003 The Korean Journal of Physiology & Pharmacology Vol.7 No.1

Cellular redox state is known to be perturbed during ischemia and that $Ca^{2+}$ and $K^2$ channels have been shown to have functional thiol groups. In this study, the properties of thiol redox modulation of the ATP-sensitive $K^2$ ($K_{ATP}$) channel were examined in rabbit ventricular myocytes. Rabbit ventricular myocytes were isolated using a Langendorff column for coronary perfusion and collagenase. Single-channel currents were measured in excised membrane patch configuration of patch-clamp technique. The thiol oxidizing agent 5,5'-dithio-bis-(2-nitro-benzoic acid) (DTNB) inhibited the channel activity, and the inhibitory effect of DTNB was reversed by dithiothreitol (disulfide reducing agent; DTT). DTT itself did not have any effect on the channel activity. However, in the patches excised from the metabolically compromised cells, DTT increased the channel activity. DTT had no effect on the inhibitory action by ATP, showing that thiol oxidation was not involved in the blocking mechanism of ATP. There were no statistical difference in the single channel conductance for the oxidized and reduced states of the channel. Analysis of the open and closed time distributions showed that DTNB had no effect on open and closed time distributions shorter than 4 ms. On the other hand, DTNB decreased the life time of bursts and increased the interburst interval. N-ethylmaleimide (NEM), a substance that reacts with thiol groups of cystein residues in proteins, induced irreversible closure of the channel. The thiol oxidizing agents (DTNB, NEM) inhibited of the $K_{ATP}$ channel only, when added to the cytoplasmic side. The results suggested that metabolism-induced changes in the thiol redox can also modulate $K_{ATP}$ channel activity and that a modulatory site of thiol redox may be located on the cytoplasmic side of the $K_{ATP}$ channel in rabbit ventricular myocytes.

Modulation of Cardiac ATP-Sensitive $K^+$ Channels Via Signal Transduction Mechanisms During Ischemic Preconditioning

Han, Jin,Kim, Nari,Seog, Dae-Hyun,Kim, Euiyong Korean Society of Life Science 2002 Journal of Life Science Vol.12 No.1

In several species, a short period of ischemic preconditioning protects the heart by reducing the size of infarcts resulting from subsequent prolonged bouts of ischemia. The mechanism by which activation of ATP-sensitive $K^+$($K_ATP$) channels could provide the memory associated with ischemic preconditioning is still under debate. Several signal transduction pathways have been implicated in the mechanisms of protection induced by ischemic preconditioning. The exact receptor-coupled pathways involved in preconditioning remain to be identified. Likely extracellular agonists are those whose circulating levels increase under conditions that activate $K_ATP$ channels; these conditions include ischemia and ischemic preconditioning. Potential physiological agonists include the following: (1) nitric oxide; (2) catecholamine; (3) adenosine; (4) acetylcholine; (5) bradykinin and (6) prostacycline. The purpose of this review was to understand the mechanism by which biological signal transduction mechanism acts as a link in one or more known receptor-mediated pathways to increase $K_ATP$ channel activity during ischemic preconditioning.

Dual Roles of Graphene Oxide To Attenuate Inflammation and Elicit Timely Polarization of Macrophage Phenotypes for Cardiac Repair

Han, Jin,Kim, Yong Sook,Lim, Min-Young,Kim, Han Young,Kong, Saerom,Kang, Mikyung,Choo, Yeon Woong,Jun, Ju Hee,Ryu, Seungmi,Jeong, Hye-yun,Park, Jooyeon,Jeong, Gun-Jae,Lee, Jong-Chan,Eom, Gwang Hyeon,A American Chemical Society 2018 ACS NANO Vol.12 No.2

<P>Development of localized inflammatory environments by M1 macrophages in the cardiac infarction region exacerbates heart failure after myocardial infarction (MI). Therefore, the regulation of inflammation by M1 macrophages and their timely polarization toward regenerative M2 macrophages suggest an immunotherapy. Particularly, controlling cellular generation of reactive oxygen species (ROS), which cause M1 differentiation, and developing M2 macrophage phenotypes in macrophages propose a therapeutic approach. Previously, stem or dendritic cells were used in MI for their anti-inflammatory and cardioprotective potentials and showed inflammation modulation and M2 macrophage progression for cardiac repair. However, cell-based therapeutics are limited due to invasive cell isolation, time-consuming cell expansion, labor-intensive and costly <I>ex vivo</I> cell manipulation, and low grafting efficiency. Here, we report that graphene oxide (GO) can serve as an antioxidant and attenuate inflammation and inflammatory polarization of macrophages <I>via</I> reduction in intracellular ROS. In addition, GO functions as a carrier for interleukin-4 plasmid DNA (IL-4 pDNA) that propagates M2 macrophages. We synthesized a macrophage-targeting/polarizing GO complex (MGC) and demonstrated that MGC decreased ROS in immune-stimulated macrophages. Furthermore, DNA-functionalized MGC (MGC/IL-4 pDNA) polarized M1 to M2 macrophages and enhanced the secretion of cardiac repair-favorable cytokines. Accordingly, injection of MGC/IL-4 pDNA into mouse MI models attenuated inflammation, elicited early polarization toward M2 macrophages, mitigated fibrosis, and improved heart function. Taken together, the present study highlights a biological application of GO in timely modulation of the immune environment in MI for cardiac repair. Current therapy using off-the-shelf material GO may overcome the shortcomings of cell therapies for MI.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2018/ancac3.2018.12.issue-2/acsnano.7b09107/production/images/medium/nn-2017-09107t_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn7b09107'>ACS Electronic Supporting Info</A></P>

Iron Oxide Nanoparticle-Mediated Development of Cellular Gap Junction Crosstalk to Improve Mesenchymal Stem Cells’ Therapeutic Efficacy for Myocardial Infarction

Han, Jin,Kim, Bokyoung,Shin, Jung-Youn,Ryu, Seungmi,Noh, Myungkyung,Woo, Jongsu,Park, Jin-Sil,Lee, Youjin,Lee, Nohyun,Hyeon, Taeghwan,Choi, Donghoon,Kim, Byung-Soo American Chemical Society 2015 ACS NANO Vol.9 No.3

<P>Electrophysiological phenotype development and paracrine action of mesenchymal stem cells (MSCs) are the critical factors that determine the therapeutic efficacy of MSCs for myocardial infarction (MI). In such respect, coculture of MSCs with cardiac cells has windowed a platform for cardiac priming of MSCs. Particularly, active gap junctional crosstalk of MSCs with cardiac cells in coculture has been known to play a major role in the MSC modification through coculture. Here, we report that iron oxide nanoparticles (IONPs) significantly augment the expression of connexin 43 (Cx43), a gap junction protein, of cardiomyoblasts (H9C2), which would be critical for gap junctional communication with MSCs in coculture for the generation of therapeutic potential-improved MSCs. MSCs cocultured with IONP-harboring H9C2 (cocultured MSCs: cMSCs) showed active cellular crosstalk with H9C2 and displayed significantly higher levels of electrophysiological cardiac biomarkers and a cardiac repair-favorable paracrine profile, both of which are responsible for MI repair. Accordingly, significantly improved animal survival and heart function were observed upon cMSC injection into rat MI models compared with the injection of unmodified MSCs. The present study highlights an application of IONPs in developing gap junctional crosstalk among the cells and generating cMSCs that exceeds the reparative potentials of conventional MSCs. On the basis of our finding, the potential application of IONPs can be extended in cell biology and stem cell-based therapies.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2015/ancac3.2015.9.issue-3/nn506732n/production/images/medium/nn-2014-06732n_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn506732n'>ACS Electronic Supporting Info</A></P>

Synthesis of uniform silica particles with controlled size by organic amine base catalysts via one-step process

Han, Jin,Yu, Taekyung,Im, Sang Hyuk Elsevier 2017 Journal of industrial and engineering chemistry Vol.52 No.-

<P><B>Abstract</B></P> <P>Uniform silica particles were synthesized by synergistic combination of sodium 4-styrene sulfonate (NaSS) anionic surfactant and organic amine base catalyst such as ethylenediamine (EDA) or diethylenetriamine (DETA). The EDA and DETA organic amine base catalysts could promote the growth reaction rate so that they produced larger silica particles compared to the NH<SUB>4</SUB>OH base catalyst because the organic amines provide more basic micro-environment near the surface of the silica particle due to multiple amine groups in a single molecule. Accordingly, the size of the silica particle was 450±12nm (NH<SUB>4</SUB>OH), 725±21nm (EDA), and 942±130nm (DETA) in similar pH conditions.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Uniform silica particles were synthesized by organic amine base catalysts. </LI> <LI> Organic amine base catalysts provide more basic micro-environment. </LI> <LI> Organic amine base catalysts promote the growth reaction rate. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Calcium Current and Background Current Activation in L-triiodothyronine Loaded Ventricular Myocytes of the Rabbit

Han. Jin,Kim. Eui-Yong,Han. Jae-Hee,Park. Choon-Ok,Hong. Seong-Geun,Leem. Chae-Hun,So. In-Suk,Ho. Won-Kyung,Earm. Yung-E,Sung. Ho-Kyung 대한생리학회 1992 대한생리학회지 Vol.26 No.2

Permissive action of thyroid hormone at the level of Ca channel and responsible mechanisms underlying thyroid hormone-induced change in myocardial contractile state and T₃-induced arrhythmias were investigated in rabbit ventricular or atrial myocytes using whole cell patch clamp technique. Single cells were isolated by Langendorff perfusion with collagenase. Cardiac myocytes were incubated in low-Cl^-,, high-K⁺ medium containing 1_μM L-triiodothyronine (T₃) at 4℃ for 2.10 hours. The calcium currrent (I_Ca) was increased in T₃ loaded cells, however, the shape of current voltage curve and reverse potential did not altered. Cyclic AMP, cyclic GMP, isoprenaline and 3-isobutyl-1-methyl-xanthine increased I_Ca in euthyroid and hyperthyroid conditions, and acetylcholine blocked the increase of I_Ca in T₃ loaded cells. The amplitude of I_Ca was much larger after perfusing cGMP than cGMP in both conditions, whereas the degree of increase of I_Ca was greater after perfusing cAMP than cGMP in T₃ loaded cells. The degree of increase of I_Ca after perfusing isoprenaline or IBMX also was greater in T₃ loaded cells than in control cells. Background current induced by isoprenaline also increased in T₃ loaded cells. The Ca release dependent inward current was increased in amplitude but its activation and inactivation time course was not changed in T₃ loaded cells. Activation of Na pump current was not changed in T₃ loaded cells. From the above results it is suggested that thyroid hormone induced increase in the contractile state of cardiac myocytes are accompanied by augmented I_Ca and the increase of Ca release from sarcoplasmic reticulum and the permissive action of thyroid hormone to catecholamines could induce arrhythmias through the increase of I_Ca and background current.

Ambivalent Representations of Nationalism and Regionalism in Early Modern Korean Art

Han Jin The Academy of Korean Studies 2008 THE REVIEW OF KOREAN STUDIES Vol.11 No.1

The fabrication of metal silicide nanodot arrays using localized ion implantation

Han, Jin,Kim, Tae-Gon,Min, Byung-Kwon,Lee, Sang Jo IOP Pub 2010 Nanotechnology Vol.21 No.48

<P>We propose a process for fabricating nanodot arrays with a pitch size of less than 25 nm. The process consists of localized ion implantation in a metal thin film on a Si wafer using a focused ion beam (FIB), followed by chemical etching. This process utilizes the etching resistivity changes of the ion beam irradiated region that result from metal silicide formation by ion implantation. To control the nanodot diameter, a threshold ion dose model is proposed using the Gaussian distribution of the ion beam intensities. The process is verified by fabricating nanodots with various diameters. The mechanism of etching resistivity is investigated via x-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES). </P>