Updated on 2024/09/18

写真a

 
MURAKAMI Shingo
 
Organization
Faculty of Science and Engineering Professor
Other responsible organization
Electrical, Electronic, and Communication Engineering Course of Graduate School of Science and Engineering, Master's Program
Electrical Engineering and Information Systems Course of Graduate School of Science and Engineering, Doctoral Program
Contact information
The inquiry by e-mail is 《here
External link

Degree

  • 博士(工学) ( 東京大学 )

  • 修士(工学) ( 東京大学 )

Education

  • 2001.3
     

    The University of Tokyo   Graduate School, Division of Engineering   doctor course   completed

  • 1998.3
     

    The University of Tokyo   Graduate School, Division of Engineering   master course   completed

  • 1996.3
     

    Kyoto University   Faculty of Engineering   graduated

Research History

  • 2019.4 - 2022.3

    自然科学研究機構岡崎共通研究施設計算科学研究センター   外部運営委員

  • 2018.4 -  

    東邦大学理学部生理学講座統合生理学分野   非常勤講師

  • 2018.4 -  

    中央大学理工学部   教授

  • 2016.4 - 2018.3

    東邦大学医学部生理学講座統合生理分野   講師

  • 2007.4 - 2016.3

    大阪大学臨床医工学融合研究教育センター   助教(兼任)

  • 2006.4 - 2016.3

    大阪大学大学院医学系研究科薬理学講座(分子・細胞薬理学)   助手(現・助教)

  • 2006.4 - 2016.3

    大阪大学大学院医学系研究科薬理学講座(分子・細胞薬理学) 助手(現・助教)

  • 2005.1 - 2006.3

    ニューメキシコ大学医学部神経内科   Research Assistant Professor

  • 2002.12 - 2005.1

    ニューメキシコ大学医学部神経内科   Research Scientist

  • 2001.4 - 2002.12

    ニューメキシコ大学医学部神経内科   Post-Doctorial Scientist

▼display all

Professional Memberships

  • 応用物理学会

  • 日本生体医工学会

  • 日本神経回路学会

  • 日本循環薬理学会

  • 日本薬理学会

  • 日本生理学会

  • 日本不整脈心電学会

  • Asia-Pacific Neural Network Society

▼display all

Research Interests

  • Physiology

  • Systemis Biology

  • 医工学

  • Pharmacology

Research Areas

  • Life Science / Biomaterials  / Biomedical engineering/Biomaterial science and engineering

  • Life Science / Neuroscience-general  / Neurophysiology/General neuroscience

  • Life Science / Clinical pharmacy  / 生理学一般

  • Informatics / Life, health and medical informatics  / 生命・健康・医療情報学

  • Life Science / Basic brain sciences  / Brain biometrics

  • Life Science / Biomedical engineering  / Biomedical engineering/Biomaterial science and engineering

  • Life Science / Pharmacology  / 薬理学一般

  • Life Science / Physiology  / 生理学一般

▼display all

Papers

  • Quantitative evaluation of virtual reality-related attention allocation through somatic P300 response Reviewed

    Kaito Kageyama, Rintaro Maki, Yasushi Nakatani, Yumie Ono, Shingo Murakami

    Advanced Biomedical Engineering   13   116 - 122   2024.4

     More details

    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.14326/abe.13.116

    researchmap

  • 光音響イメージングによるカルシウム濃度計測のための吸光試薬のスクリーニングシステム Reviewed

    山本 勇志, 興野 大輝, 五味 涼太, 庄司 一郎, 村上 慎吾

    電子情報通信学会論文誌 D   J107-D ( 4 )   265 - 272   2024.4

     More details

    Authorship:Last author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)  

    researchmap

  • Measuring the Permittivity of Liposome and Yeast Using a 3D-printed Electrode-replaceable Measuring Cell Reviewed

    Yuji KAGEYAMA, Haruna SUEOKA, Akira KIMURA, Masaki SATO, Akira ITO, Tetsuro HORIE, Genki OGATA, Yasuaki EINAGA, Hiroaki SUZUKI, Shingo MURAKAMI

    Advanced Biomedical Engineering   13   90 - 99   2024

     More details

    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Japanese Society for Medical and Biological Engineering  

    DOI: 10.14326/abe.13.90

    researchmap

  • Event-related Potentials based Evaluation of attention allocation while watching VR Reviewed

    Advanced Biomedical Engineering   11   1 - 9   2022.1

     More details

    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    researchmap

  • Different voltage dependence of ICaL blockade in nonselective IKr blockers causes their opposite effects on early afterdepolarization in drug-induced arrhythmia Reviewed

    Akira Kimura, Shingo Murakami

    Journal of Pharmacological Sciences   147 ( 1 )   95 - 103   2021.9

     More details

    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:September 2021,  

    researchmap

  • Computer modeling defines the system driving a constant current crucial for homeostasis in the mammalian cochlea by integrating unique ion transports Reviewed International journal

    Fumiaki Nin, Takamasa Yoshida, Shingo Murakami, Genki Ogata, Satoru Uetsuka, Samuel Choi, Katsumi Doi, Seishiro Sawamura, Hidenori Inohara, Shizuo Komune, Yoshihisa Kurachi, Hiroshi Hibino

    npj Systems Biology and Applications   3 ( 24 )   1 - 10   2017.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nature Publishing  

    The cochlear lateral wall-an epithelial-like tissue comprising inner and outer layers-maintains +80 mV in endolymph. This endocochlear potential supports hearing and represents the sum of all membrane potentials across apical and basolateral surfaces of both layers. The apical surfaces are governed by K+ equilibrium potentials. Underlying extracellular and intracellular [K+] is likely controlled by the "circulation current," which crosses the two layers and unidirectionally flows throughout the cochlea. This idea was conceptually reinforced by our computational model integrating ion channels and transporters; however, contribution of the outer layer's basolateral surface remains unclear. Recent experiments showed that this basolateral surface transports K+ using Na+, K+-ATPases and an unusual characteristic of greater permeability to Na+ than to other ions. To determine whether and how these machineries are involved in the circulation current, we used an in silico approach. In our updated model, the outer layer's basolateral surface was provided with only Na+, K+-ATPases, Na+ conductance, and leak conductance. Under normal conditions, the circulation current was assumed to consist of K+ and be driven predominantly by Na+, K+-ATPases. The model replicated the experimentally measured electrochemical properties in all compartments of the lateral wall, and endocochlear potential, under normal conditions and during blocking of Na+, K+-ATPases. Therefore, the circulation current across the outer layer's basolateral surface depends primarily on the three ion transport mechanisms. During the blockage, the reduced circulation current partially consisted of transiently evoked Na+ flow via the two conductances. This work defines the comprehensive system driving the circulation current.

    DOI: 10.1038/s41540-017-0025-0

    PubMed

    researchmap

  • アセチルコリン感受性カリウム電流における短期脱感作のシミュレーション解析 Reviewed

    村上慎吾, 稲野辺厚, 倉智嘉久

    心電図   35 ( 4 )   245 - 257   2016.10

     More details

    Authorship:Lead author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:日本心電学会  

    Acetylcholine (ACh) increases the amplitude of cardiac K+ current (IK.ACh) through activation of the muscarinic K+ (KACh) channel, but the amplitude gradually decreases to a quasi-steady-state level within seconds. This phenomenon, known as short-term desensitization, is believed to play a role in cellular adaptation to external input. However, the precise mechanism and physiological role of short-term desensitization is still unclear. In the present review, we introduced our experimental and theoretical studies on the mechanisms underlying short-term desensitization of IK.ACh. In atrial myocytes, short-term desensitization features the unique dose responses of the transient and quasi-steady state IK.ACh, effects of ACh preperfusion and recovery from short-term desensitization. In simulation analysis, two conditions are required for the mathematical IK.ACh model to reconstitute short-term desensitization. The first condition is distinct muscarinic receptors (M2Rs) with different affinities for ACh, which conferred an IK.ACh response over a wide range of ACh concentrations. The second condition is 2 distinct KACh channels with different affinities for the G-proteinβγsubunit, which contributes to reconstitution of the temporal behavior of IK.ACh. Under these conditions, the model quantitatively reproduced the unique properties of short-term desensitization observed in experiments. Furthermore, the present model conferred vagal escape on the mathematical action potential models of sinus node cells. Therefore, 2 different populations of KACh channels and M2Rs may be responsible for short-term desensitization and vagal escape at nodal cells.

    DOI: 10.5105/jse.35.245

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2016139097

  • The unique electrical properties in an extracellular fluid of the mammalian cochlea; their functional roles, homeostatic processes, and pathological significance Reviewed

    Fumiaki Nin, Takamasa Yoshida, Seishiro Sawamura, Genki Ogata, Takeru Ota, Taiga Higuchi, Shingo Murakami, Katsumi Doi, Yoshihisa Kurachi, Hiroshi Hibino

    PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY   468 ( 10 )   1637 - 1649   2016.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    The cochlea of the mammalian inner ear contains an endolymph that exhibits an endocochlear potential (EP) of +80 mV with a [K+] of 150 mM. This unusual extracellular solution is maintained by the cochlear lateral wall, a double-layered epithelial-like tissue. Acoustic stimuli allow endolymphatic K+ to enter sensory hair cells and excite them. The positive EP accelerates this K+ influx, thereby sensitizing hearing. K+ exits from hair cells and circulates back to the lateral wall, which unidirectionally transports K+ to the endolymph. In vivo electrophysiological assays demonstrated that the EP stems primarily from two K+ diffusion potentials yielded by [K+] gradients between intracellular and extracellular compartments in the lateral wall. Such gradients seem to be controlled by ion channels and transporters expressed in particular membrane domains of the two layers. Analyses of human deafness genes and genetically modified mice suggested the contribution of these channels and transporters to EP and hearing. A computational model, which reconstitutes unidirectional K+ transport by incorporating channels and transporters in the lateral wall and connects this transport to hair cell transcellular K+ fluxes, simulates the circulation current flowing between the endolymph and the perilymph. In this model, modulation of the circulation current profile accounts for the processes leading to EP loss under pathological conditions. This article not only summarizes the unique physiological and molecular mechanisms underlying homeostasis of the EP and their pathological relevance but also describes the interplay between EP and circulation current.

    DOI: 10.1007/s00424-016-1871-0

    Web of Science

    researchmap

  • The unique ion permeability profile of cochlear fibrocytes and its contribution to establishing their positive resting membrane potential Reviewed

    Takamasa Yoshida, Fumiaki Nin, Shingo Murakami, Genki Ogata, Satoru Uetsuka, Samuel Choi, Takashi Nakagawa, Hidenori Inohara, Shizuo Komune, Yoshihisa Kurachi, Hiroshi Hibino

    PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY   468 ( 9 )   1609 - 1619   2016.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Eukaryotic cells exhibit negative resting membrane potential (RMP) owing to the high K+ permeability of the plasma membrane and the asymmetric [K+] between the extracellular and intracellular compartments. However, cochlear fibrocytes, which comprise the basolateral surface of a multi-layer epithelial-like tissue, exhibit a RMP of +5 to +12 mV in vivo. This positive RMP is critical for the formation of an endocochlear potential (EP) of +80 mV in a K+-rich extracellular fluid, endolymph. The epithelial-like tissue bathes fibrocytes in a regular extracellular fluid, perilymph, and apically faces the endolymph. The EP, which is essential for hearing, represents the potential difference across the tissue. Using in vivo electrophysiological approaches, we describe a potential mechanism underlying the unusual RMP of guinea pig fibrocytes. The RMP was + 9.0 +/- 3.7 mV when fibrocytes were exposed to an artificial control perilymph (n = 28 cochleae). Perilymphatic perfusion of a solution containing low [Na+] (1 mM) markedly hyperpolarized the RMP to -31.1 +/- 11.2 mV (n = 10; p < 0.0001 versus the control, TukeyKramer test after one-way ANOVA). Accordingly, the EP decreased. Little change in RMP was observed when the cells were treated with a high [K+] of 30 mM (+ 10.4 +/- 2.3 mV; n= 7; p = 0.942 versus the control). During the infusion of a low [Cl-] solution (2.4 mM), the RMP moderately hyperpolarized to -0.9 +/- 3.4 mV (n = 5; p < 0.01 versus the control), although the membranes, if governed by Cl-permeability, should be depolarized. These observations imply that the fibrocyte membranes are more permeable to Na+ than K+ and Cl-, and this unique profile and [Na+] gradient across the membranes contribute to the positive RMP.

    DOI: 10.1007/s00424-016-1853-2

    Web of Science

    researchmap

  • Mechanisms of astrocytic K+ clearance and swelling under high extracellular K+ concentrations Reviewed

    Shingo Murakami, Yoshihisa Kurachi

    JOURNAL OF PHYSIOLOGICAL SCIENCES   66 ( 2 )   127 - 142   2016.3

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER JAPAN KK  

    In response to the elevation of extracellular K+ concentration ([K+](out)), astrocytes clear excessive K+ to maintain conditions necessary for neural activity. K+ clearance in astrocytes occurs via two processes: K+ uptake and K+ spatial buffering. High [K+](out) also induces swelling in astrocytes, leading to edema and cell death in the brain. Despite the importance of astrocytic K+ clearance and swelling, the underlying mechanisms remain unclear. Here, we report results from a simulation analysis of astrocytic K+ clearance and swelling. Astrocyte models were constructed by incorporating various mechanisms such as intra/extracellular ion concentrations of Na+, K+, and Cl-, cell volume, and models of Na, K-ATPase, Na-K-Cl cotransporter (NKCC), K-Cl cotransporter, inwardly-rectifying K+ (KIR) channel, passive Cl- current, and aquaporin channel. The simulated response of astrocyte models under the uniform distribution of high [K+](out) revealed significant contributions of NKCC and Na, K-ATPase to increases of intracellular K+ and Cl- concentrations, and swelling. Moreover, we found that, under the non-uniform distribution of high [K+](out), KIR channels localized at synaptic clefts absorbed excess K+ by depolarizing the equivalent potential of K+ (E-K) above membrane potential, while K+ released through perivascular KIR channels was enhanced by hyperpolarizing E-K and depolarizing membrane potential. Further analysis of simulated drug effects revealed that astrocyte swelling was modulated by blocking each of the ion channels and transporters. Our simulation analysis revealed controversial mechanisms of astrocytic K+ clearance and swelling resulting from complex interactions among ion channels and transporters.

    DOI: 10.1007/s12576-015-0404-5

    Web of Science

    researchmap

  • Invariance in current dipole moment density across brain structures and species: Physiological constraint for neuroimaging Reviewed

    Shingo Murakami, Yoshio Okada

    NEUROIMAGE   111   49 - 58   2015.5

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Although anatomical constraints have been shown to be effective for MEG and EEG inverse solutions, there are still no effective physiological constraints. Strength of the current generator is normally described by the moment of an equivalent current dipole Q. This value is quite variable since it depends on size of active tissue. In contrast, the current dipole moment density q, defined as Q per surface area of active cortex, is independent of size of active tissue. Here we studied whether the value of q has a maximum in physiological conditions across brain structures and species. We determined the value due to the primary neuronal current (q(primary)) alone, correcting for distortions due to measurement conditions and secondary current sources at boundaries separating regions of differing electrical conductivities. The values were in the same range for turtle cerebellum(0.56-1.48 nAm/mm(2)), guinea pig hippocampus (0.30-1.34 nAm/mm(2)), and swine neocortex (0.18-1.63 nAm/mm(2)), rat neocortex (similar to 2.2 nAm/mm(2)), monkey neocortex (similar to 0.40 nAm/mm(2)) and human neocortex (0.16- 0.77 nAm/mm(2)). Thus, there appears to be a maximum value across the brain structures and species (1-2 nAm/mm(2)). The empirical values closely matched the theoretical values obtained with our independently validated neural network model (1.6-2.8 nAm/mm(2) for initial spike and 0.7-3.1 nAm/mm(2) for burst), indicating that the apparent invariance is not coincidental. Our model study shows that a single maximum value may exist across a wide range of brain structures and species, varying in neuron density, due to fundamental electrical properties of neurons. The maximum value of qprimary may serve as an effective physiological constraint for MEG/EEG inverse solutions. (C) 2015 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.neuroimage.2015.02.003

    Web of Science

    researchmap

  • Short-term desensitization of muscarinic K+ current in the heart Reviewed

    Shingo Murakami, Atsushi Inanobe, Yoshihisa Kurachi

    Biophysical Journal   105 ( 6 )   1515 - 1525   2013.11

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biophysical Society  

    researchmap

  • 内耳内リンパ液の特殊電位環境の成立機構の理解

    日比野浩, 任書晃, 村上慎吾, 土井勝美, 鈴木敏弘, 久育男, 倉智嘉久

    日本耳鼻咽喉科学会会報   116 ( 2 )   60 - 68   2013.2

     More details

    Language:Japanese   Publisher:日本耳鼻咽喉科学会  

    CiNii Books

    researchmap

  • Computational model of a circulation current that controls electrochemical properties in the mammalian cochlea Reviewed

    Fumiaki Nin, Hiroshi Hibino, Shingo Murakami, Toshihiro Suzuki, Yasuo Hisa, Yoshihisa Kurachi

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   109 ( 23 )   9191 - 9196   2012.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATL ACAD SCIENCES  

    Sound-evoked mechanical stimuli permit endolymphatic K+ to enter sensory hair cells. This transduction is sensitized by an endocochlear potential (EP) of +80 mV in endolymph. After depolarizing the cells, K+ leaves hair cells in perilymph, and it is then circulated back to endolymph across the lateral cochlear wall. In theory, this process entails a continuous and unidirectional current carried by apical K+ channels and basolateral K+ uptake transporters in both the marginal cell and syncytial layers of the lateral wall. The transporters regulate intracellular and extracellular [K+], allowing the channels to form K+ diffusion potentials across each of the two layers. These diffusion potentials govern the EP. What remains uncertain is whether these transport mechanisms accumulating across diverse cell layers make up a continuous circulation current in the lateral wall and how this current might affect the characteristics of the endolymph. To address this question, we developed an electrophysiological model that incorporates channels and transporters of the lateral wall and channels of hair cells that derive a circulation current. The simulation replicated normal experimental EP values and reproduced experimentally measured changes in the EP and intra-and extracellular [K+] in the lateral wall when different transporters and channels were blocked. The model predicts that, under these different conditions, the circulation current's contribution to the EP arises from different sources. Finally, our model also accurately simulated EP loss in a mouse model of a chloride channelopathy associated with deafness.

    DOI: 10.1073/pnas.1120067109

    Web of Science

    researchmap

  • Transmural dispersion of repolarization determines scroll wave behavior during ventricular tachyarrhythmias - a simulation study - Reviewed

    Ryo Haraguchi, Takashi Ashihara, Tsunetoyo Namba, Kunichika Tsumoto, Shingo Murakami, Yoshihisa Kurachi, Takanori Ikeda, Kazuo Nakazawa

    Circulation Journal   75 ( 1 )   80 - 88   2011

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Japanese Ciruculation Society  

    Background: Ventricular tachyarrhythmia is the leading cause of sudden cardiac death, and scroll wave re-entry is known to underlie this condition. Class III antiarrhythmic drugs are commonly used worldwide to treat ventricular tachyarrhythmias
    however, these drugs have a proarrhythmic adverse effect and can cause Torsade de Pointes or ventricular fbrillation. Transmural dispersion of repolarization (TDR) has been suggested to be a strong indicator of ventricular tachyarrhythmia induction. However, the role of TDR during sustained scroll wave re-entry is poorly understood. The purpose of the present study was to investigate how TDR affects scroll wave behavior and to provide a novel analysis of the mechanisms that sustain tachyarrhythmias, using computer simulations. Methods and Results: Computer simulations were carried out to quantify the TDR and QT interval under a variety of Iks and Ikr during transmural conduction. Simulated scroll wave re-entries were done under a variety of Iks and Ikr in a ventricular wall slab model, and the scroll wave behavior and the flament dynamics (3-dimensional organizing center) were analyzed. A slight increase in TDR, but not in the QT interval, refected antiarrhythmic properties resulting from the restraint of scroll wave breakup, whereas a marked increase in TDR was proarrhythmic, as a result of scroll wave breakup. Conclusions: The TDR determines the sustainment of ventricular tachyarrhythmias, through control of the scroll wave flament dynamics.

    DOI: 10.1253/circj.CJ-10-0071

    Scopus

    PubMed

    researchmap

  • フィジオームとシステムバイオロジー

    村上慎吾, 倉智嘉久

    生体の科学   61 ( 4 )   364 - 371   2010.8

     More details

    Authorship:Lead author   Language:Japanese   Publisher:医学書院  

    researchmap

  • Inwardly rectifying potassium channels: their structure, function and physiological roles Reviewed International journal

    Hiroshi Hibino, Atsushi Inanobe, Kazuharu Furutani, Shingo Murakami, Ian Findlay, Yoshihisa Kurachi

    Physiological Review   90 ( 1 )   291 - 366   2010.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Physiological Scoiety  

    Inwardly rectifying K(+) (Kir) channels allow K(+) to move more easily into rather than out of the cell. They have diverse physiological functions depending on their type and their location. There are seven Kir channel subfamilies that can be classified into four functional groups: classical Kir channels (Kir2.x) are constitutively active, G protein-gated Kir channels (Kir3.x) are regulated by G protein-coupled receptors, ATP-sensitive K(+) channels (Kir6.x) are tightly linked to cellular metabolism, and K(+) transport channels (Kir1.x, Kir4.x, Kir5.x, and Kir7.x). Inward rectification results from pore block by intracellular substances such as Mg(2+) and polyamines. Kir channel activity can be modulated by ions, phospholipids, and binding proteins. The basic building block of a Kir channel is made up of two transmembrane helices with cytoplasmic NH(2) and COOH termini and an extracellular loop which folds back to form the pore-lining ion selectivity filter. In vivo, functional Kir channels are composed of four such subunits which are either homo- or heterotetramers. Gene targeting and genetic analysis have linked Kir channel dysfunction to diverse pathologies. The crystal structure of different Kir channels is opening the way to understanding the structure-function relationships of this simple but diverse ion channel family.

    DOI: 10.1152/physrev.00021.2009

    PubMed

    researchmap

  • Cellular modelling: experiments and simulation to develop the physiological model for G-protein control of cardiac muscarinic K+ channels Reviewed

    Shingo Murakami, Shingo Suzuki, Masaru Ishii, Atsushi Inanobe, Yoshihisa Kurachi

    Philosophical Transactions of the Royal Society A   368 ( 1921 )   2983 - 3000   2010.1

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Royal Society  

    researchmap

  • 薬物誘発性不整脈の発生危険度予測システムの開発 Reviewed

    村上慎吾, 鈴木慎悟, 上島豊, 野村泰伸, 倉智嘉久

    生体医工学   48 ( 1 )   106 - 114   2010.1

     More details

    Authorship:Lead author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:日本生体医工学会  

    researchmap

  • Development of drug-induced arrhythmia prediction system

    Shingo Murakami, Shingo Suzuki, Yutaka Ueshima, Taishin Nomura, Yoshihisa Kurachi

    Transactions of Japanese Society for Medical and Biological Engineering   48 ( 1 )   106 - 114   2010

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    A number of drugs in clinical use and during development have had to be withdrawn because of their proarrhythmic side effects. These otherwise promising compounds are a risk for patients and force the pharmaceutical industry to bear enormous costs. For assessment of potential risk of drug-induced cardiac arrhythmia, the effects of a drug on the Human ether-a-go-go related gene (HERG) channel expressed in either mammalian cells or Xenopus oocytes, and the prolongation of action potential duration (APD) and QT interval in animals, are now routinely measured. However, there are enough examples to indicate that these tests are not accurate or sufficient to assess the proarrhythmic risk of drugs. Therefore, further development of prediction methods for risk assessment is awaited to increase safety in drug usage in clinics and in new drug development. An in silico strategy has particular merits for this purpose, because, different from purely experimental approaches, it can easily deal with the diverse actions of the drugs. The in silico assessment of a drug's proarrhythmic risk requires a method that provides quantitative and comprehensive comparison of the effects of different forms of I kr-blockade upon APDs and transmural dispersion of repolarization (TDR). Previously, we have developed various cardiac action potential models, as well as a novel risk-assessment method based on W IKS, two-dimensional maps of APD and TDR. In the present paper, we introduce a new prediction system based on cardiac action potential simulation and model database. This system consists of registered models, accumulated calculation results, computer cluster and client software. Various procedures for simulation and analysis can be executed on the web. The developed prediction system may be a useful tool to predict the risk of drug-induced arrhythmia.

    Scopus

    researchmap

  • In silico study on the effects of I_<Kr> and I_<Kur> block kinetics on prolongation of human action potential

    MURAKAMI Shingo, TSUJIMAE Kenji, SUZUKI Shingo, KURACHI Yoshihisa

    Japanese Journal of Electrocardiology   29 ( 2 )   126 - 132   2009.4

     More details

    Language:Japanese   Publisher:The Japanese Society of Electrocardiology  

    DOI: 10.5105/jse.29.126

    CiNii Books

    researchmap

    Other Link: http://search.jamas.or.jp/link/ui/2009199477

  • 貫壁性再分極時間の差が増悪すると3次元スパイラルリエントリーの分裂が促進される シミュレーションモデルによる検討

    原口 亮, 芦原 貴司, 八尾 武憲, 難波 経豊, 藤堂 貴弘, 村上 慎吾, 倉智 嘉久, 池田 隆徳, 中沢 一雄

    心電図   29 ( Suppl.1 )   S - 86   2009.3

     More details

    Language:Japanese   Publisher:(一社)日本不整脈心電学会  

    researchmap

  • In silico risk assessment for drug-induction of cardiac arrhythmia Reviewed

    Shingo Suzuki, Shingo Murakami, Kenji Tsujimae, Ian Findlay, Yoshihisa Kurachi

    Progress in Biophysics & Molecular Biology   98 ( 1 )   52 - 60   2008.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier  

    researchmap

  • 3次元心室壁モデルにおけるスパイラルリエントリーのin silicoフィラメント動態解析~致死的不整脈防御機構としての心室較差の電気生理学的意義~ Reviewed

    芦原貴司, 藤堂貴弘, 難波経豊, 村上慎吾, 倉智嘉久, 中沢一雄

    生体医工学   46 ( 6 )   660 - 666   2008.11

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:日本生体医工学会  

    researchmap

  • In silico prediction of the chemical block of human Ether-a-go-go-Related Gene (hERG) K+ current Reviewed

    Atsushi Inanobe, Narutoshi Kamiya, Shingo Murakami, Yoshifumi Fukunishi, Haruki Nakamura, Yoshihisa Kurachi

    Journal of Physiological Sciences   58 ( 7 )   459 - 470   2008.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer  

    researchmap

  • 貫壁性再分極時間の差が頻脈性不整脈の興奮伝播ダイナミクスに与える影響について

    原口 亮, 芦原 貴司, 鈴木 慎悟, 難波 経豊, 藤堂 貴弘, 八尾 武憲, 村上 慎吾, 倉智 嘉久, 池田 隆徳, 中沢 一雄

    心電図   28 ( 5 )   466 - 466   2008.10

     More details

    Language:Japanese   Publisher:(一社)日本不整脈心電学会  

    researchmap

  • クレフト電位仮説による貫壁性心室較差の再現に関する理論的研究

    鈴木 慎悟, 芦原 貴司, 原口 亮, 村上 慎吾, 倉智 嘉久, 中沢 一雄

    心電図   28 ( 5 )   525 - 525   2008.10

     More details

    Language:Japanese   Publisher:(一社)日本不整脈心電学会  

    researchmap

  • Scroll wave dynamics in tachyarrhythmia: Roles of transmural gradient. Reviewed

    Haraguchi R, Ashihara T, Yao T, Todo T, Namba T, Murakami S, Kurachi Y, Nakazawa K

    Transactions of the Japanese Society for Medical and Biological Engineering (JSMBE).   46   480 - 481   2008.7

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    researchmap

  • In silico study on the effects of I-Kur block kinetics on prolongation of human action potential after atrial fibrillation-induced electrical remodeling Reviewed

    Kenji Tsujimae, Shingo Murakami, Yoshihisa Kurachi

    AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY   294 ( 2 )   H793 - H800   2008.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER PHYSIOLOGICAL SOC  

    Pharmacological treatment with various antiarrhythmic agents for the termination or prevention of atrial fibrillation (AF) is not yet satisfactory. This is in part because the drugs may not be sufficiently selective for the atrium, and they often cause ventricular arrhythmias. The ultrarapid-delayed rectifying potassium current (I-Kur) is found in the atrium but not in the ventricle, and it has been recognized as a potentially promising target for anti-AF drugs that would be without ventricular proarrhythmia. Several new agents that specifically block I-Kur have been developed. They block I-Kur in a voltage- and time-dependent manner. Here we use mathematical models of normal and electrically remodeled human atrial action potentials to examine the effects of the blockade kinetics of I-Kur on atrial action potential duration (APD). It was found that after AF remodeling, an I-Kur blocker with fast onset can effectively prolong APD at any stimulus frequency, whereas a blocker with slow onset prolongs APD in a frequency- dependent manner only when the recovery is slow. The results suggest that the voltage and time dependence of IKur blockade should be taken into account in the testing of anti-AF drugs. This modeling study suggests that a simple voltage-clamp protocol with a short pulse of similar to 10 ms at 1 Hz may be useful to identify the effective anti-AF drugs among various I-Kur blockers.

    DOI: 10.1152/ajpheart.01229.2007

    Web of Science

    researchmap

  • Physiological modulation of voltage-dependent inactivation in the cardiac muscle L-type calcium channel: A modelling study Reviewed

    Ian Findlay, Shingo Suzuki, Shingo Murakami, Yoshihisa Kurachi

    PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY   96 ( 1-3 )   482 - 498   2008.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    The inactivation of the L-type Ca2+ current is composed of voltage-dependent and calcium -dependent mechanisms. The relative contribution of these processes is still under dispute and the idea that the voltage-dependent inactivation could be subject to further modulation by other physiological processes had been ignored. This study sought to model physiological modulation of inactivation of the current in cardiac ventricular myocytes, based upon the recent detailed experimental data that separated total and voltage-dependent inactivation (VDI) by replacing extracellular Ca2+ with Mg2+ and monitoring L-type Ca2+ channel behaviour by outward K+ current flowing through the channel in the absence of inward current flow. Calcium -dependent inactivation (CDI) was based upon Ca2+ influx and formulated from data that was recorded during beta-adrenergic stimulation of the myocytes. Ca2+ influx and its competition with non-selective monovalent cation permeation were also incorporated into channel permeation in the model. The constructed model could closely reproduce the experimental Ba2+ and Ca2+ current results under basal condition where no beta-stimulation was added after a slight reduction of the development of fast voltage-dependent inactivation with depolarization. The model also predicted that under beta-adrenereic stimulation voltage-dependent inactivation is lost and calcium-dependent inactivation largely compensates it. The developed model thus will be useful to estimate the respective roles of VDI and CDI of L-type Ca2+ channels in various physiological and pathological conditions of the heart which would otherwise be difficult to show experimentally. (C) 2007 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.pbiomolbio.2007.07.002

    Web of Science

    researchmap

  • Mechanisms of action of antiarrhythmic drugs Reviewed

    Shingo Murakami, Yoshihisa Kurachi

    Electrical Diseases of the Heart: Genetics, Mechanisms, Treatment, Prevention   133 - 144   2008

     More details

    Authorship:Lead author   Language:English   Publishing type:Part of collection (book)   Publisher:Springer London  

    Antiarrhythmic drugs have been used as an effective measure to treat or prevent tachyarrhythmias including ventricular tachycardia and fibrillation in clinics for a long time. Arrhythmias refer to changes from the normal sequence of electrical impulses and conduction, causing abnormal heart rhythms. They can be classified into two categories: bradyarrhythmias and tachyarrhythmias. Both can make the heart pump less effectively and, more seriously, cause sudden death. Possible treatments include electrical defibrillation, radio frequency ablation, implantable cardioverter defibrillators, artificial pacemakers, and medication. All these are used to prevent or terminate arrhythmias. Among them, arrhythmia medication is a nonsurgical and effective treatment and its major target has been tachyarrhythmias, mainly in the ventricle, including ventricular tachycardia and fibrillation. Of course, recently treatment of atrial tachyarrhythmias such as atrial fibrillation is also one of the major interests. However, its application may cause serious adverse effects.1 Since usage of antiarrhythmic drugs tended to rely on clinicians' experience and to be based on clinical practice, the effects of antiarrhythmic drugs had been understood empirically. Accumulated studies on the mechanism of antiarrhythmic agents, however, have provided much basic understanding of drug action, especially on the electrophysiological properties of cardiac excitation. This will not only help clinicians to select proper antiarrhythmic drugs, but will also help in the development of new antiarrhythmic drugs. © 2008 Springer-Verlag London Limited.

    DOI: 10.1007/978-1-84628-854-8_7

    Scopus

    researchmap

  • In silico study on the effects of I-kur block kinetics on prolongation of human action potential after atrial fibrillation-induced electrical-remodeling Reviewed

    Kenji Tsujimae, Shingo Muramami, Yoshihisa Kurachi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106 ( 2 )   261P - 261P   2008

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPANESE PHARMACOLOGICAL SOC  

    Web of Science

    researchmap

  • Microstructure-Based Monte Carlo Simulation of Ca2+ Dynamics Evoking Cardiac Calcium Channel Inactivation Reviewed

    Kawazu Toshihiro, Murakami Shingo, Adachi-Akahane Satomi, Findlay Ian, Ait-Haddou Rachid, Kurachi Yoshihisa, Nomura Taishin

    The Journal of Physiological Sciences   58 ( 7 )   471 - 480   2008

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PHYSIOLOGICAL SOCIETY OF JAPAN  

    Ca2+ dynamics underlying cardiac excitation-contraction coupling are essential for heart functions. In this study, we constructed microstructure-based models of Ca2+ dynamics to simulate Ca2+ influx through individual L-type calcium channels (LCCs), an effective Ca2+ diffusion within the cytoplasmic space and in the dyadic space, and the experimentally observed calcium-dependent inactivation (CDI) of the LCCs induced by local and global Ca2+ sensing. The models consisted of LCCs with distal and proximal Ca2+ (Calmodulin-Ca2+ complex) binding sites. In one model, the intracellular space was organelle-free cytoplasmic space, and the other was with a dyadic space including sarcoplasmic reticulum membrane. The Ca2+ dynamics and CDI of the LCCs in the model with and without the dyadic space were then simulated using the Monte Carlo method. We first showed that an appropriate set of parameter values of the models with effectively extra-slow Ca2+ diffusion enabled the models to reproduce major features of the CDI process induced by the local and global sensing of Ca2+ near LCCs as measured with single and two spatially separated LCCs by Imredy and Yue (Neuron. 1992;9:197-207). The effective slow Ca2+ diffusion might be due to association and dissociation of Ca2+ and Calmodulin (CaM). We then examined how the local and global CDIs were affected by the presence of the dyadic space. The results suggested that in microstructure modeling of Ca2+ dynamics in cardiac myocytes, the effective Ca2+ diffusion under CaM-Ca2+ interaction, the nanodomain structure of LCCs for detailed CDI, and the geometry of subcellular space for modeling dyadic space should be considered.<br>

    DOI: 10.2170/physiolsci.RP013208

    researchmap

  • Frequency dependent effects of various IKr blockers on cardiac action potential duration in a human atrial model Reviewed

    Kenji Tsujimae, Shingo Suzuki, Shingo Murakami, Yoshihisa Kurachi

    American Journal of Physiology - Heart and Circulatory Physiology   293 ( 1 )   H660 - H669   2007.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Physiological Scoiety  

    researchmap

  • Contributions of principal neocortical neurons to magnetoencephalography (MEG) and electroencephalography (EEG) signals Reviewed

    Shingo Murakami, Yoshio Okada

    Journal of Physiology   575 ( 3 )   925 - 936   2006.11

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Physiological Society  

    researchmap

  • Contribution of ionic currents to magnetoencephalography (MEG) and electroencephalography (EEG) signals generated by guinea-pig CA3 slices Reviewed

    S Murakami, A Hirose, YC Okada

    JOURNAL OF PHYSIOLOGY-LONDON   553 ( 3 )   975 - 985   2003.12

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:CAMBRIDGE UNIV PRESS  

    A mathematical model was used to analyse the contributions of different types of ionic currents in the pyramidal cells of longitudinal CA3 slices to the magnetic fields and field potentials generated by this preparation. Murakami et al. recently showed that a model based on the work of Traub et al. provides a quantitatively accurate account of the basic features of three types of empirical data (magnetic fields outside the slice, extracellular field potentials within the slice and intracellular potentials within the pyramidal neurons) elicited by stimulations of the soma and apical dendrites. This model was used in the present study to compute the net current dipole moment (Q) due to each of the different voltage- and ligand-gated channels in the cells in the presence of fast GABA(A) inhibition. These values of Q are proportional to the magnetic field and electrical potential far away from the slice. The intrinsic conductances were found to be more important than the synaptic conductances in determining the shape and magnitude of Q. Among the intrinsic conductances, the sodium (g(Na)) and delayed-rectifier potassium (g(K(DR))) channels were found to produce sharp spikes. The high-threshold calcium channel (g(Ca)) and C-type potassium channel (g,(c)) primarily determined the overall current waveforms. The roles Of g(Ca) and g(K(C)) were independent of small perturbations in these channel densities in the apical and basal dendrites. A combination of g(Na), g(K(DR)), g(Ca), and g(K(C)) accounted for most of the evoked responses, except for later slow components, which were primarily due to synaptic channels.

    DOI: 10.1113/jphysiol.2003.051144

    Web of Science

    researchmap

  • Physiological origins of evoked magnetic fields and extracellular field potentials produced by guinea-pig CA3 hippocampal slices Reviewed

    S Murakami, TS Zhang, A Hirose, YC Okada

    JOURNAL OF PHYSIOLOGY-LONDON   544 ( 1 )   237 - 251   2002.10

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    This study examined whether evoked magnetic fields and intra- and extracellular potentials from longitudinal CA3 slices of guinea-pig can be interpreted within a single theoretical framework that incorporates ligand- and voltage-sensitive conductances in the dendrites and soma of the pyramidal cells. The 1991 CA3 mathematical model of R. D. Traub is modified to take into account the asymmetric branching patterns of the apical and basal dendrites of the pyramidal cells. The revised model accounts for the magnitude and waveform of the bi- and triphasic magnetic fields evoked by somatic and apical stimulations, respectively, in the slice in the absence of fast inhibition (blocked by 0.1 mm picrotoxin). The revised model also accounts for selective effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA), which block the potassium channels of A and C type, respectively, on the slow wave of the magnetic fields. Furthermore, the model correctly predicts the laminar profiles of field potential as well as intracellular potentials in the pyramidal cells produced by two classes of cells - those directly activated and those indirectly (synaptically) activated by the applied external stimulus. The intracellular potentials in this validated model reveal that the spikes and slow waves of the magnetic fields are generated in or near the soma and apical dendrites, respectively. These results demonstrate that a single theoretical framework couched within the modern concepts of cellular physiology provides a unified account of magnetic fields outside the slice, extracellular potentials within the slice and intracellular potentials of the pyramidal cells for CA3.

    DOI: 10.1113/jphysiol.2002.027094

    Web of Science

    researchmap

▼display all

MISC

  • 不整脈の基質とトリガーによるリスク評価 Invited

    村上 慎吾

    BIO Clinica   35 ( 8 )   48 - 51   2020.7

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

    researchmap

  • 蝸牛らせん靱帯の持続的脱分極性膜電位に関するin silico解析

    任 書晃, 吉田 崇正, 村上 慎吾, 緒方 元気, 上塚 学, 小宗 静男, 倉智 嘉久, 日比野 浩

    日本生理学雑誌   78 ( 2 )   46 - 47   2016.3

     More details

    Language:Japanese   Publisher:(一社)日本生理学会  

    researchmap

  • 内耳蝸牛側壁のK+輸送システムに立脚した内リンパ液高電位の成立機構

    任 書晃, 吉田 崇正, 村上 慎吾, 倉智 嘉久, 日比野 浩

    Audiology Japan   59 ( 2 )   109 - 118   2016

     More details

    Language:Japanese   Publisher:Japan Audiological Society  

    <p> Endolymph, a unique extracellular fluid in the cochlea of the inner ear, exhibits a highly positive potential of +80 mV. This so-called endocochlear potential (EP), which is indispensable for hearing, originates from the lateral cochlear wall. The lateral wall, which comprises the stria vascularis and its neighboring spiral ligament, is likely made up of two epithelial layers. By using electrophysiological and theoretical approaches, we have shown that the EP depends on the K+ dynamics in the extra/intracellular compartments of the lateral wall. Of importance, the K+ environment seems to be controlled by the unidirectional K+ transport throughout the cochlea. Moreover, the results of our recent study suggest that of the several K+-transport molecules expressed in the lateral wall, only Na+, K+-ATPase is likely to be involved in driving the unidirectional K+ transport. These findings will contribute not only to elucidation of the mechanism underlying hearing, but also that of the pathophysiological processes involved in deafness caused by impairment of the EP.</p>

    DOI: 10.4295/audiology.59.109

    researchmap

  • Theoretical and experimental analysis of ototoxic mechanism in the spiral ligament fibrocytes by multi-level simulation with ion transports in the cochlea

    任書晃, 吉田崇正, 吉田崇正, 村上慎吾, 上塚学, 上塚学, 緒方元気, 倉智嘉久, 日比野浩

    日本薬理学雑誌   147 ( 2 )   80-83 (J-STAGE) - 83   2016

     More details

    Language:Japanese   Publisher:公益社団法人 日本薬理学会  

    空気の振動である音は,内耳蝸牛に存在する音の感覚細胞である有毛細胞を振動させる.この時,有毛細胞の毛に存在するイオンチャネルが開口し,常時+80 mVを示す特殊な内リンパ液からイオンが流入する.この「内リンパ液高電位」は,有毛細胞の興奮に不可欠であり,蝸牛側壁の血管条が成立させる.Na&lt;sup&gt;+&lt;/sup&gt;,K&lt;sup&gt;+&lt;/sup&gt;,2Cl&lt;sup&gt;-&lt;/sup&gt;共輸送体(NKCC)やNa&lt;sup&gt;+&lt;/sup&gt;,K&lt;sup&gt;+&lt;/sup&gt;-ATPaseの阻害薬は,内リンパ液高電位を低下させることで,薬剤性難聴を惹起することが報告されているが,その電位低下のメカニズムは明らかにされていなかった.我々はこれまでに,血管条に発現するNKCCとNa&lt;sup&gt;+&lt;/sup&gt;,K&lt;sup&gt;+&lt;/sup&gt;-ATPaseが制御する内リンパ液高電位成立機構を電気生理学的手法により示し,さらに蝸牛内の多階層イオン輸送モデル「Nin-Hibino-Kurachi(NHK)model」の構築とコンピュータシミュレーションによって,阻害薬を経動脈的に投与した時に起こる内リンパ液高電位低下のメカニズムを説明した.血管条に隣接し,その一部と一体化しているらせん靭帯を構成する線維細胞にも,NKCCとNa&lt;sup&gt;+&lt;/sup&gt;,K&lt;sup&gt;+&lt;/sup&gt;-ATPaseが発現していることが知られているが,薬剤性難聴時のこれらの関与は不明である.近年我々は,らせん靭帯ではおもにNa&lt;sup&gt;+&lt;/sup&gt;,K&lt;sup&gt;+&lt;/sup&gt;-ATPaseが,K&lt;sup&gt;+&lt;/sup&gt;輸送とK&lt;sup&gt;+&lt;/sup&gt;濃度バランスに寄与すること,そしてNKCCはほとんど機能していないことを明らかにした.これらに基づいて,NHKモデルを改訂した.今後シミュレーションを行うことにより,輸送体阻害薬の経動脈投与の実験結果を正確に再現することが期待される.

    DOI: 10.1254/fpj.147.80

    CiNii Books

    J-GLOBAL

    researchmap

Awards

  • Best research award

    2023.9   Measuring the permittivity of liposome and yeast using a 3D printed electrode-replaceable measuring cell

    Yuuji Kageyama, Haruna Sueoka, Akira Kimura, Masaki Sato, Akira Ito, Tetsuro Horie, Genki Ogata, Yasuaki Einaga, Hiroaki Suzuki, Shingo Murakami

  • 日本生体医工学会関東支部若手研究者発表会2022優秀論文発表賞

    2022.12   日本生体医工学会   誘電スペクトロスコピーにおける微生物の誘電率計測

    影山湧二, 木村暁, 伊東章, 堀江哲郎, 緒方元気, 栄長泰明, 鈴木宏明, 村上慎吾

  • Best research award

    2021.9   Quantitative Evaluation of VR Immersion in 2D and 3D Images Using Event-Related Potentials

    Ryo Ogawa, Kaito Kageyama, Yasushi Nakatani, Yumie Ono, Shingo Murakami

Research Projects

  • Predicting risk by assessing substrate and trigger for drug-induced arrhythmia

    Grant number:19K07106  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)  Chuo University

    Murakami Shingo

      More details

    Grant amount: \4290000 ( Direct Cost: \3300000 、 Indirect Cost: \990000 )

    In the present study, to predict the different risks of drug-induced arrhythmia under various IKr blockers, we investigated the mechanism of pharmacological effects on the repolarization reserve and early afterdepolarization (EAD) by using the O'Hara-Rudy human ventricular myocyte model, three drug models (amiodarone, bepridil, terfenadine), and hypothetical drug models. We rigorously redefined repolarization reserve and constructed a new quantitative risk assessment method based on this redefinition. In addition, it was shown that the difference of the drug effect on L-type calcium current (ICaL) affected the generation frequency of EAD. Based on the mechanisms identified above, we proposed a protocol for risk prediction and confirmed its validity.

    researchmap

  • Simulation analysis on astrocytic K+ buffering

    Grant number:25460331  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)  Osaka University

    Murakami Shingo

      More details

    Grant amount: \5200000 ( Direct Cost: \4000000 、 Indirect Cost: \1200000 )

    In response to elevation of extracellular K+ concentration ([K+]out), astrocytes clear excessive extracellular K+ to maintain proper environment for neural activity. Here we conducted simulation analysis on the mechanisms of the astrocytic K+ clearance and swelling. Astrocyte models were constructed by incorporating into a compartment model various mechanisms. Simulated response of astrocyte models to high [K+]out revealed significant contributions of NKCC and Na,K-ATPase to the increases of the intracellular K+ and Cl- concentrations, and swelling. Moreover, we show that the KIR channel localized at synaptic cleft absorbs the excessive K+, while the K+ release through KIR channel localized at perivascular is enhanced. Further analysis of simulated drug effects shows that K+ uptake, K+ release and swelling can be modulated differently by blocking each of the ion channels and transporters.

    researchmap

  • Search for new antiarrhythmic drugs based on inhibition of trigger in atrial fibrillation

    Grant number:22790251  2010 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)  Osaka University

    MURAKAMI Shingo

      More details

    Grant amount: \3900000 ( Direct Cost: \3000000 、 Indirect Cost: \900000 )

    In this study, in order to facilitate the development of new antiarrhythmic drugs specific for atrial fibrillation, we studied the potential of TRPM4 channel inhibitors antiarrhythmic drugs. TRPM4 channel can be activated by elavated intracellular Ca^<2+> con(as) cen(new) tration and therefore can be triggers for atrial fibrillation, Since TRPM4 channels are not functional in the human ventricular, selective inhibitors of TRPM4 channels are expected to cause limited side effect in the ventricular. By using the human atrial model and TRPM4 channel model, we showed that inhibitors of TRPM4 channel may suppress atrial fibrillation and may be a good candidate for new antiarrhythmic drugs.

    researchmap

  • Studies on the structure-activity relationship on pharmacological modulations of potassium channels

    Grant number:20249012  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)  Osaka University

    KURACHI Yoshihisa, INANOBE Atsushi, HIBINO Hiroshi, MURAKAMI Shingo, FURUTANI Kazuharu

      More details

    Grant amount: \50700000 ( Direct Cost: \39000000 、 Indirect Cost: \11700000 )

    Ion channel functions are modulated by the drugs. However, the mechanisms underling drug actions are often not well understood. In this study, we examined the mechanisms of drug actions in inward-rectifier potassium channels and voltage-dependent potassium channel. Our studies reveal structural bases of drug-channel interactions and their functional alterations in potassium channel. Moreover, our results provide better understandings of their clinical efficacy or undesirable side effects, and shed light on the rational development of pharmacological agents.

    researchmap

  • Development of mathematical model of a Human atrial myocyte to evaluate new antiarrhythmic drugs for atrial fibrillation

    Grant number:20790206  2008 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)  Osaka University

    MURAKAMI Shingo

      More details

    Grant amount: \4290000 ( Direct Cost: \3300000 、 Indirect Cost: \990000 )

    In this study, I have developed a mathematical model of a Human atrial myocyte. Since characteristics of atrial myocyte differ among animals, the developed model allows us to evaluate effects of antiarrhythmic drug specifically for human. Although human atrial myocytes are difficult to obtain for experiments, by using the developed model, we can examine effects of virtual drug profiles in human atrial myocytes. The developed model may improve efficiency of drug development.

    researchmap

  • Physiological regulation of G protein signaling by RGS proteins

    Grant number:17079005  2005 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Priority Areas  Osaka University

    KURACHI Yoshihisa, INANOBE Atsushi, MURAKAMI Shingo, FURUTANI Kazuharu, ISHII Masaru

      More details

    Grant amount: \72900000 ( Direct Cost: \72900000 )

    Trimeric G proteins transmit extracellular signals to regulate the intracellular effectors. The spatiotemporal regulation of this signal closely links to the cellular responses. In this study, we addressed the regulation of G protein signaling by RGS proteins, the mathematical models of G protein signaling and the structure-function relationship of K^+ channel to analyze the physiological regulation of G protein signaling.

    researchmap

▼display all