Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
External link
竹内 綾子
Degree
-
Ph.D. ( Kyoto University )
Research Interests
-
Bリンパ球
-
心筋細胞
-
フィジオーム
-
Ca2+ダイナミクス
-
mitochondria
-
細胞生理学
-
システム生理学
Education
-
Kyoto University 薬学研究科 博士後期課程 医療薬科学専攻
2000.4 - 2003.3
Country： Japan
-
京都大学 薬学研究科 修士課程 医療薬科学専攻
1998.4 - 2000.3
-
Kyoto University
1994.4 - 1998.3
Research History
-
Okayama University Department of Physiology and Biophysics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
2025.4
-
University of Fukui Department of Integrative and Systems Physiology, Faculty of Medical Sciences Associate Professor
2017.4 - 2025.3
-
福井大学医学部 形態機能医科学講座 統合生理学 特命助教
2013.9 - 2017.3
-
京都大学医学研究科 生体制御医学講座 細胞機能制御学 助教
2009.4
-
米国ロックフェラー大学 Research Associate
2008.4
-
米国ロックフェラー大学 Postdoctoral Associate
2007.4
-
京都大学医学研究科 生体制御医学講座 細胞機能制御学 助手
2005.12
-
京都大学医学研究科 産学官連携助手
2005.8
-
京都大学医学研究科 産学官連携研究員
2004.4
-
日本学術振興会特別研究員(PD)
2003.4
-
日本学術振興会特別研究員(DC)
2002.4
Professional Memberships
-
Society of General Physiologists
2013
-
Biophysical Society
2006
-
Physiological Society of Japan
2005
-
The Pharmaceutical Society of Japan
1998
Committee Memberships
-
日本生理学会 JPS編集委員
2023.4
Committee type：Academic society
-
日本生理学会編集・広報委員
2022.4
-
第9回アジア・オセアニア生理学会連合大会FAOPS2019 一般演題査読委員
2018.10 - 2019.3
Committee type：Academic society
-
第9回アジア・オセアニア生理学会連合大会FAOPS2019 JGPポスターアワード委員
2018.9 - 2019.3
Committee type：Academic society
-
日本生理学会 評議員
2011.3
-
日本薬学会医療薬科学部会 若手世話人
2009.4 - 2013.8
Papers
-
A simulation study on the role of mitochondria-sarcoplasmic reticulum Ca2+ interaction in cardiomyocyte energetics during exercise. Reviewed International journal
Ayako Takeuchi, Satoshi Matsuoka
The Journal of physiology 603 ( 18 ) 4921 - 4949 2025.9
-
Molecular logic of salt taste reception in special reference to transmembrane channel-like 4 (TMC4) Reviewed
Yoichi Kasahara, Masataka Narukawa, Ayako Takeuchi, Makoto Tominaga, Keiko Abe, Tomiko Asakura
The Journal of Physiological Sciences 72 ( 1 ) 2022.12
-
Spatial and Functional Crosstalk between the Mitochondrial Na+-Ca2+ Exchanger NCLX and the Sarcoplasmic Reticulum Ca2+ Pump SERCA in Cardiomyocytes Reviewed
Ayako Takeuchi, Satoshi Matsuoka
International Journal of Molecular Sciences 2022.7
-
Physiological and pathophysiological roles of mitochondrial Na+-Ca2+ exchanger, NCLX, in hearts. Reviewed International journal
Ayako Takeuchi, Satoshi Matsuoka
Biomolecules 11 ( 12 ) 2021.12
-
TMC4 is a novel chloride channel involved in high-concentration salt taste sensation. Reviewed
Yoichi Kasahara, Masataka Narukawa, Yoshiro Ishimaru, Shinji Kanda, Chie Umatani, Yasunori Takayama, Makoto Tominaga, Yoshitaka Oka, Kaori Kondo, Takashi Kondo, Ayako Takeuchi, Takumi Misaka, Keiko Abe, Tomiko Asakura
The Journal of Physiological Sciences 71 ( 1 ) 23 - 23 2021.8
-
Minor contribution of NCX to Na+-Ca2+ exchange activity in brain mitochondria Reviewed
Ayako Takeuchi, Satoshi Matsuoka
Cell Calcium 96 102386 - 102386 2021.3
-
Membrane current evoked by mitochondrial Na+-Ca2+ exchange in mouse heart. Reviewed
Mohammed M Islam, Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiological Sciences 70 ( 1 ) 24 - 24 2020.4
-
Integration of mitochondrial energetics in heart with mathematical modelling. Reviewed International journal
Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiology 2020.2
-
Physiological functions of mitochondrial Na+-Ca2+ exchanger, NCLX, in lymphocytes. Reviewed International journal
Ayako Takeuchi, Bongju Kim, Satoshi Matsuoka
Cell Calcium 85 102114 - 102114 2020.1
-
Uncovering the arrhythmogenic potential of TRPM4 activation in atrial-derived HL-1 cells using novel recording and numerical approaches Reviewed
Yaopeng Hu, Yubin Duan, Ayako Takeuchi, Lin Hai-Kurahara, Jun Ichikawa, Keizo Hiraishi, Tomohiro Numata, Hiroki Ohara, Gentaro Iribe, Michio Nakaya, Masayuki X. Mori, Satoshi Matsuoka, Genshan Ma, Ryuji Inoue
Cardiovascular Research 113 ( 10 ) 1243 - 1255 2017.8
-
A simulation study on the constancy of cardiac energy metabolites during workload transition Reviewed
Ryuta Saito, Ayako Takeuchi, Yukiko Himeno, Nobuya Inagaki, Satoshi Matsuoka
The Journal of Physiology 594 ( 23 ) 6929 - 6945 2016.12
-
Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage. Reviewed
Sakamaki K, Ishii TM, Sakata T, Takemoto K, Takagi C, Takeuchi A, Morishita R, Takahashi H, Nozawa A, Shinoda H, Chiba K, Sugimoto H, Saito A, Tamate S, Satou Y, Jung SK, Matsuoka S, Koyamada K, Sawasaki T, Nagai T, Ueno N
Biochimica et Biophysica Acta 1863 ( 11 ) 2766 - 2783 2016.11
-
Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia Reviewed
Kenichi Sasaki, Takeru Makiyama, Yoshinori Yoshida, Yimin Wuriyanghai, Tsukasa Kamakura, Suguru Nishiuchi, Mamoru Hayano, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Mihoko Kawamura, Seiko Ohno, Hideki Itoh, Ayako Takeuchi, Satoshi Matsuoka, Masaru Miura, Naokata Sumitomo, Minoru Horie, Shinya Yamanaka, Takeshi Kimura
PLOS ONE 11 ( 10 ) e0164795 2016.10
-
Roles of the mitochondrial Na+-Ca2+ exchanger, NCLX, in B lymphocyte chemotaxis Reviewed
Bongju Kim, Ayako Takeuchi, Masaki Hikida, Satoshi Matsuoka
Scientific Reports 6 28378 2016.6
-
Physiological study on the Ca2+ crosstalk between mitochondria-sarcoplasmic/endoplasmic reticulum Invited Reviewed
TAKEUCHI Ayako
Membrane 41 ( 5 ) 215 - 220 2016
-
Inhibition of mitochondrial Na+-Ca2+ exchange by CGP-37157 attenuates BCR-mediated apoptosis in DT40 B lymphocytes Reviewed
Bongju Kim, Ayako Takeuchi, Satoshi Matsuoka, Jong Ho Lee, Yong Cheol Shin, Dong-Wook Han
Journal of the Korean Physical Society 67 ( 11 ) 1915 - 1919 2015.12
-
The destiny of Ca2+ released by mitochondria Reviewed
Ayako Takeuchi, Bongju Kim, Satoshi Matsuoka
The Journal of Physiological Sciences 65 ( 1 ) 11 - 24 2015.1
-
Role of mitochondrial Na+-Ca2+ exchanger, NCLX, in the generation of cardiac automaticity Reviewed
TAKEUCHI Ayako, MATSUOKA Satoshi
Jpn. J. Electrocardiology 34 ( 2 ) 69 - 81 2014
-
Identification of chemicals inducing cardiomyocyte proliferation in developmental stage-specific manner with pluripotent stem cells Reviewed
Hideki Uosaki, Ajit Magadum, Kinya Seo, Hiroyuki Fukushima, Ayako Takeuchi, Yasuaki Nakagawa, Kara White Moyes, Genta Narazaki, Koichiro Kuwahara, Michael Laflamme, Satoshi Matsuoka, Norio Nakatsuji, Kazuwa Nakao, Chulan Kwon, David A. Kass, Felix B. Engel, Jun K. Yamashita
Circulation: Cardiovascular Genetics 6 ( 6 ) 624 - 633 2013.12
-
The mitochondrial Na+-Ca2+ exchanger, NCLX, regulates automaticity of HL-1 cardiomyocytes Reviewed
Ayako Takeuchi, Bongju Kim, Satoshi Matsuoka
Scientific Reports 3 2766 2013.9
-
Mitochondria Na+-Ca2+ exchange in cardiomyocytes and lymphocytes Reviewed
Bongju Kim, Ayako Takeuchi, Orie Koga, Masaki Hikida, Satoshi Matsuoka
Advances in Experimental Medicine and Biology 961 193 - 201 2013
-
NHE-1 blockade reversed changes in calcium transient in myocardial slices from isoproterenol-induced hypertrophied rat left ventricle Reviewed
Hiroshi Hattori, Daisuke Takeshita, Ayako Takeuchi, Bongju Kim, Munetaka Shibata, Satoshi Matsuoka, Koji Obata, Shinichi Mitsuyama, Guo-Xing Zhang, Miyako Takaki
Biochemical and Biophysical Research Communications 419 ( 2 ) 431 - 435 2012.3
-
Pivotal role of mitochondrial Na+-Ca2+ exchange in antigen receptor mediated Ca2+ signalling in DT40 and A20 B lymphocytes Reviewed
Bongju Kim, Ayako Takeuchi, Orie Koga, Masaki Hikida, Satoshi Matsuoka
The Journal of Physiology 590 ( 3 ) 459 - 474 2012.2
-
Impairment of Ubiquitin-Proteasome System by E334K cMyBPC Modifies Channel Proteins, Leading to Electrophysiological Dysfunction Reviewed
Udin Bahrudin, Kumi Morikawa, Ayako Takeuchi, Yasutaka Kurata, Junichiro Miake, Einosuke Mizuta, Kaori Adachi, Katsumi Higaki, Yasutaka Yamamoto, Yasuaki Shirayoshi, Akio Yoshida, Masahiko Kato, Kazuhiro Yamamoto, Eiji Nanba, Hiroko Morisaki, Takayuki Morisaki, Satoshi Matsuoka, Haruaki Ninomiya, Ichiro Hisatome
Journal of Molecular Biology 413 ( 4 ) 857 - 878 2011.11
-
Efficient and Scalable Purification of Cardiomyocytes from Human Embryonic and Induced Pluripotent Stem Cells by VCAM1 Surface Expression Reviewed
Hideki Uosaki, Hiroyuki Fukushima, Ayako Takeuchi, Satoshi Matsuoka, Norio Nakatsuji, Shinya Yamanaka, Jun K. Yamashita
PLOS ONE 6 ( 8 ) e23657 2011.8
-
心筋細胞イオンチャネルモデル(京都モデル)とその展開
竹内 綾子, 松岡 達
医学のあゆみ 238 ( 3 ) 217 - 221 2011
-
Systems biology of cell volume regulation Reviewed
TAKEUCHI Ayako, NOMA Akinori
Seibutsu Butsuri 50 ( 5 ) 248 - 251 2010
-
Visualizing the mapped ion pathway through the Na, K-ATPase pump Reviewed
Ayako Takeuchi, Nicolas Reyes, Pablo Artigas, David C. Gadsby
Channels 3 ( 6 ) 383 - 386 2009.11
-
Increased O2 consumption in excitation-contraction coupling in hypertrophied rat heart slices related to increased Na+-Ca2+ exchange activity Reviewed
Juichiro Shimizu, Daisuke Yamashita, Hiromi Misawa, Kiyoe Tohne, Satoshi Matsuoka, Bongju Kim, Ayako Takeuchi, Chikako Nakajima-Takenaka, Miyako Takaki
The Journal of Physiological Sciences 59 ( 1 ) 63 - 74 2009.1
-
Peering into an ATPase ion pump with single-channel recordings Reviewed
David C. Gadsby, Ayako Takeuchi, Pablo Artigas, Nicolas Reyes
Philosophical Transactions of The Royal Society B-Biological Sciences 364 ( 1514 ) 229 - 238 2009.1
-
The ion pathway through the opened Na(+),K(+)-ATPase pump Reviewed
Ayako Takeuchi, Nicolas Reyes, Pablo Artigas, David C. Gadsby
Nature 456 ( 7220 ) 413 - 416 2008.11
-
Simulation analysis of intracellular Na+ and Cl- homeostasis during beta 1-adrenergic stimulation of cardiac myocyte Reviewed
Masanori Kuzumoto, Ayako Takeuchi, Hiroyuki Nakai, Chiaki Oka, Akinori Noma, Satoshi Matsuoka
Progress in Biophysics and Molecular Biology 96 ( 1-3 ) 171 - 186 2008.1
-
Role of Ca2+ transporters and channels in the cardiac cell volume regulation Reviewed
A. Takeuchi, S. Tatsumi, N. Sarai, K. Terashima, S. Matsuoka, A. Noma
Annals of the New York Academy of Sciences 1099 377 - 382 2007
-
Ionic mechanisms of cardiac cell swelling induced by blocking Na+/K+ pump as revealed by experiments and simulation Reviewed
Ayako Takeuchi, Shuji Tatsumi, Nobuaki Sarai, Keisuke Terashima, Satoshi Matsuoka, Akinori Noma
Journal of General Physiology 128 ( 5 ) 495 - 507 2006.11
-
Modelling Cl- homeostasis and volume regulation of the cardiac cell Reviewed
K Terashima, A Takeuchi, N Sarai, S Matsuoka, EB Shim, CH Leem, A Noma
Philosophical Transactions of the Royal Society A-Mathematical Physical and Engineering Sciences 364 ( 1842 ) 1245 - 1265 2006.5
-
Gene expression variance based on random sequencing in rat remnant kidney Reviewed
N Horiba, S Masuda, A Takeuchi, H Saito, M Okuda, KI Inui
Kidney International 66 ( 1 ) 29 - 45 2004.7
-
Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney: roles of organic ion transporters, rOAT1 rOAT3 and rOCT2 Reviewed
Y Habu, Yano, I, A Takeuchi, H Saito, M Okuda, A Fukatsu, K Inui
Biochemical Pharmacology 66 ( 6 ) 1107 - 1114 2003.9
-
Cloning and characterization of a novel Na+-dependent glucose transporter (NaGLT1) in rat kidney Reviewed
N Horiba, S Masuda, A Takeuchi, D Takeuchi, M Okuda, K Inui
Journal of Biological Chemistry 278 ( 17 ) 14669 - 14676 2003.4
-
Decreased Function of Genetic Variants, Pro283Leu and Arg287Gly, in Human Organic Cation Transporter hOCT1 Reviewed
Ayako Takeuchi, Hideyuki Motohashi, Masahiro Okuda, Ken-ichi Inui
Drug Metabolism and Pharmacokinetics 18 ( 6 ) 409 - 412 2003
-
Multispecific substrate recognition of kidney-specific organic anion transporters OAT-K1 and OAT-K2 Reviewed
A Takeuchi, S Masuda, H Saito, T Abe, K Inui
Journal of Pharmacology and Experimental Therapeutics 299 ( 1 ) 261 - 267 2001.10
-
Role of kidney-specific organic anion transporters in the urinary excretion of methotrexate Reviewed
A Takeuchi, S Masuda, H Saito, T Doi, K Inui
Kidney International 60 ( 3 ) 1058 - 1068 2001.9
-
TAKEUCHI Ayako, MASUDA Satohiro, SAITO Hideyuki, INUI Ken-ichi
Drug Metabolism and Pharmacokinetics 16 ( 2 ) 134 - 139 2001
-
Trans-stimulation effects of folic acid derivatives on methotrexate transport by rat renal organic anion transporter, OAT-K1 Reviewed
A Takeuchi, S Masuda, H Saito, Y Hashimoto, K Inui
Journal of Pharmacology and Experimental Therapeutics 293 ( 3 ) 1034 - 1039 2000.6
-
Takeuchi Ayako, Masuda Satohiro, Saito Hideyuki, Inui Ken-ichi
Drug Metabolism and Pharmacokinetics 15 96 - 97 2000
-
Functional analysis of rat renal organic anion transporter OAT-K1: Bidirectional methotrexate transport in apical membrane Reviewed
Satohiro Masuda, Ayako Takeuchi, Hideyuki Saito, Yukiya Hashimoto, Ken-Ichi Inui
FEBS Letters 459 ( 1 ) 128 - 132 1999.10
-
Cloning and functional characterization of a new multispecific organic anion transporter, OAT-K2, in rat kidney Reviewed
S Masuda, K Ibaramoto, A Takeuchi, H Saito, Y Hashimoto, K Inui
Molecular Pharmacology 55 ( 4 ) 743 - 752 1999.4
Books
-
生理学実習書
松岡 達, 竹内 綾子（ Role： Contributor , 心室筋細胞興奮収縮連関）
南江堂 2013
-
Patch Clamp Techniques-From beginning to advanced protocols-
MATSUOKA Satoshi, TAKEUCHI Ayako（ Role： Contributor , Giant Patch and Macro Patch）
Springer Protocols 2012
-
トランスポートソームの世界―膜輸送研究の源流から未来へ―
竹内 綾子（ Role： Contributor , 輸送体の構造解析―Na,K-ATPase pumpを例に）
京都廣川書店 2011
-
MOLECULAR SYSTEM BIOENERGETICS Energy for life
Matsuoka S, Jo H, Kuzumoto M, Takeuchi A, Saito R, Noma A（ Role： Contributor , Modeling energetics of ion transport, membrane sensing and system biology of the heart）
WILEY-VCH 2007
-
Control and Diseases of Sodium Dependent Transport Proteins and Ion Channels
Masuda S, Takeuchi A, Saito H, Hashimoto Y, Inui K（ Role： Contributor , Tubular localization and drug recognition of organic anion transporters OAT-K1 and OAT-K2）
Elsevier Science B. V. 2000
MISC
-
Enhanced ATP consumption during tetanic contraction and homeostatic mechanisms of the cellular energy metabolism in ventricular myocytes: A simulation study
Yukiko Himeno, Ayako Takeuchi, Futoshi Toyoda, Yixin Zhang, Akinori Noma, Akira Amano
The Journal of Physiological Sciences 75 ( suppl1 ) 669 - 669 2025.3
-
Role of mitochondria-sarcoplasmic reticulum Ca2+ coupling in cardiac energy metabolism during exercise
Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiological Sciences 75 ( suppl1 ) 381 - 381 2025.3
-
Physiological impacts of spatial distribution of mitochondrial Ca 2+ transporters in cardiomyocytes
Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiological Sciences 74 ( suppl2 ) S43 - S43 2024.5
-
Contribution of KATP channels activated in ventricular myocytes to repolarization: a simulation study
Yukiko Himeno, Hiroto Nomura, Wenli Zhang, Yixin Zhang, Yuttamol Muangkram, Ayako Takeuchi, Akinori Noma, Akira Amano
The Journal of Physiological Sciences 74 ( suppl2 ) S138 - S138 2024.5
-
Impact of mitochondrial Ca2+ dynamics on cardiomyocyte function
Satoshi Matsuoka, Ayako Takeuchi, Yukari Takeda
The Journal of Physiological Sciences 73 ( suppl1 ) S11 - S11 2023.5
-
Distinct characteristics of mitochondrial Ca2+ dynamics in mouse heart and brain
Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiological Sciences 73 ( suppl1 ) S59 - S59 2023.5
-
Contributions of NCLX and NCX to mitochondrial Na+ -Ca 2+ exchange in mouse brain
Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiological Sciences 71 ( suppl1 ) S133 - S133 2021.8
-
The mitochondrial Na+-Ca2+ exchanger is involved in automaticity of murine sinoatrial nodal cells
Yukari Takeda, Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiological Sciences 69 ( suppl1 ) S106 - S106 2019.6
-
Evaluation of effects of empagliflozin on mouse ventricular myocytes
Hinako Suzuki, Takuma Yoshizawa, Shunsuke Aoki, Saki Watanabe, Yukari Takeda, Ayako Takeuchi and Satoshi Matsuoka
The Journal of Physiological Sciences 69 ( suppl1 ) S172 - S172 2019.6
-
A theoretical study on the roles of Ca2+ in the energy metabolite stability during cardiac workload transition
Ayako Takeuchi, Ryuta Saito, Yukiko Himeno, Satoshi Matsuoka
Biophysical Journal 112 ( 3 ) 131A - 131A 2017.2
-
A simulation study on Ca2+ regulation of energy metabolism in cardiac mitochondria
Satoshi Matsuoka, Ayako Takeuchi, Ryuta Saito, Yukiko Himeno
The Journal of Physiological Sciences 67 ( suppl1 ) S23 - S23 2017.1
-
Physiome study on the roles of mitochondria-endoplasmic reticulum Ca2+ crosstalk in lymphocytes
Ayako Takeuchi, Bongju Kim, Satoshi Matsuoka
The Journal of Physiological Sciences 67 ( suppl1 ) S43 - S43 2017.1
-
Involvement of vitamin D receptor and its related genes in the generation of rhythmic Ca transient in murine atrial myocyte-derived cell line HL-1
Takuya Murata, Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiological Sciences 67 ( suppl1 ) S133 - S133 2017.1
-
Contribution of Ca2+ crosstalk between mitochondria and sarcoplasmic reticulum to the cardiac pacemaker activity
Ayako Takeuchi, Satoshi Matsuoka
Transactions of Japanese Society for Medical and Biological Engineering 52 80 - OS-81 2014.8
-
Role of mitochondrial NCX on CXCL12-induced chemotaxis in A20 B lymphocytes
Bongju Kim, Ayako Takeuchi, Satoshi Matsuoka
Biophysical Journal 104 ( 2 ) 112A - 112A 2013.1
-
Mitochondrial NCX controls directional migration of B lymphocyte
Bongju Kim, Ayako Takeuchi, Satoshi Matsuoka
The Journal of Physiological Sciences 63 S136 - S136 2013
-
Theoretical analysis of mitochondrial NCX (NCLX) -mediated regulation of cardiac automaticity
Ayako Takeuchi, Bongju Kim, Satoshi Matsuoka
The Journal of Physiological Sciences 63 S120 - S120 2013
-
Role of mitochondrial Na-Ca exchange on BCR-mediated Ca2+ signalling in B Lymphocytes
Bongju Kim, Ayako Takeuchi, Orie Koga, Masaki Hikida, Satoshi Matsuoka
Biophysical Journal 102 ( 3 ) 662A - 662A 2012.1
-
Gating ion translocation through the Na,K-ATPase pump
Natascia Vedovato, Ayako Takeuchi, Pablo Artigas, Nicolas Reyes, David C. Gadsby
Biophysical Journal 102 ( 3 ) 407A - 407A 2012.1
-
Visualizing the ion pathway through the Na, K pump
Ayako Takeuchi, Nicolas Reyes, Pablo Artigas, David Gadsby
The Journal of Physiological Sciences 60 S78 - S78 2010
-
Integration of phosphate analogs with palytoxin-bound Na,K-ATPase pump-channels
Ayako Takeuchi, David C. Gadsby
The Journal of Physiological Sciences 59 489 - 489 2009
-
The ion pathway through the Na,K-ATPase pump
David C. Gadsby, Ayako Takeuchi, Nicolas Reyes, Pablo Artigas
The Journal of Physiological Sciences 59 95 - 95 2009
-
A novel glucose transporter NaGLT 1 mediates low-affinity Na+-dependent uptake of fructose as well as glucose in rat kidney.
N Horiba, S Masuda, A Takeuchi, D Takeuchi, M Okuda, K Inui
Journal of the American Society of Nephrology 14 57A - 57A 2003.11
-
バンコマイシン誘発急性腎障害からの回復過程における有機イオントランスポータ群の発現変動
竹内 綾子, 道下 孝恒, 増田 智先, 奥田 真弘, 乾 賢一
薬剤学 = Journal of Pharmaceutical Science and Technology, Japan 63 106 - 106 2003.3
-
高尿酸血症モデルラットにおける腎尿細管薬物輸送活性と有機イオントランスポーターの発現量変動
土生 康司, 矢野 育子, 竹内 綾子, 齋藤 秀之, 乾 賢一
日本薬学会年会要旨集 122年会 ( 4 ) 57 - 57 2002.3
Presentations
-
フィジオーム研究で明らかになった心筋細胞の 膜興奮－収縮－代謝連関の動的メカニズム Invited
竹内綾子
第46回生体膜と薬物の相互作用シンポジウム 2025.11.7
-
数理モデル解析からひも解く オルガネラCa2+輸送体群による心筋エネルギー代謝制御 Invited
竹内綾子
第98回日本生化学会大会 2025.11.4
-
心筋刺激頻度増大時の膜興奮－収縮－エネルギー代謝連関におけるミトコンドリアNa+-Ca2+交換の役割 Invited
竹内綾子
生理研研究会（生体電気研究会 ー不整脈・心電学研究における基礎・臨床・医工学の融合新分野の創生） 2025.7.11
-
A Physiome study on the role of Ca2+ interaction between mitochondria-sarcoplasmic reticulum in cardiomyocyte energetics Invited
Takeuchi A.
ICMS (Ion Channel Modulation Symposium) 2025 Japan 2025.5.29
-
Impact of Ca2+ crosstalk between mitochondria and sarcoplasmic reticulum in cardiomyocyte during workload transition Invited
Takeuchi A.
XXV World Congress of the International Society for Heart Research 2025.5.13
-
Enhanced ATP consumption during tetanic contraction and homeostatic mechanisms of the cellular energy metabolism in ventricular myocytes: A simulation study
HimenoY., Takeuchi A., Toyoda F., Zhang Y., Muangkram Y., Noma A., Amano A.
2025.3.19
-
Role of mitochondria-sarcoplasmic reticulum Ca2+ coupling in cardiac energy metabolism during exercise
Takeuchi A., Matsuoka S.
2025.3.17
-
心筋細胞連続EAD発射によるエネルギー代謝破綻のコンピュータシミュレーション解析2
野間昭典, 姫野友紀子, 豊田太, Zhang Yixin, 竹内綾子, 天野晃
近畿生理学談話会 2024.11.23
-
心筋細胞連続EAD発射によるエネルギー代謝破綻のコンピュータシミュレーション解析1
姫野友紀子, 豊田太, Zhang Yixin, 竹内綾子, 野間昭典, 天野晃
近畿生理学談話会 2024.11.23
-
仕事量増大時の心エネルギー代謝における ミトコンドリア-筋小胞体Ca2+連関の役割
竹内綾子, 松岡達
生理研研究会 2024.10.11
-
Theoretical analyses of the roles of mitochondrial Ca2+ dynamics during exercise using an integrated model of human ventricular myocyte
Ayako Takeuchi, Satoshi Matsuoka
2024 Cardiac Physiome Workshop 2024.9.12
-
ミトコンドリアCa2+輸送体の局在－心筋細胞機能連関に関するフィジオーム研究 Invited
竹内綾子, 松岡達
第18回トランスポーター研究会 2024.6.2
-
Contribution of KATP channels activated in ventricular myocytes to repolarization: a simulation study
Yukiko Himeno, Hiroto Nomura, Wenli Zhang, Yixin Zhang, Yuttamol, Muangkram, Ayako Takeuchi, Akinori Noma, Akira Amano
2024.3.29
-
Physiological impact of spatial distribution of mitochondrial Ca2+ transporters Invited
Ayako Takeuchi, Satoshi Matsuoka
2024.3.28
-
Roles of mitochondrial Ca2+ dynamics during cardiac workload transition Invited
Ayako Takeuchi, Satoshi Matsuoka
10th FAOPS Congress 2023.11.2
-
Roles of mitochondrial Ca2+ dynamics in cardiomyocyte function-A physiome study Invited
Ayako Takeuchi
ICMS (Ion Channel Modulation Symposium) 2023 Japan 2023.5.17
-
Distinct characteristics of mitochondrial Ca2+ dynamics in mouse heart and brain Invited
Ayako Takeuchi, Satoshi Matsuoka
日本生理学会 第100回記念大会 2023.3.16
-
Impact of mitochondrial Ca2+ dynamics on cardiomyocyte function Invited
Satoshi Matsuoka, Ayako Takeuchi, Yukari Takeda
日本生理学会 第100回記念大会 2023.3.14
-
心筋細胞におけるミトコンドリアNa+-Ca2+交換輸送体NCLXと筋小胞体Ca2+ポンプSERCAの構造的連関とその生理的役割
Ayako Takeuchi, Satoshi Matsuoka
生理研研究会 2022.10.13
-
A simulation study on cardiac mitochondrial energetics during ischemia and reperfusion Invited
Satoshi Matsuoka, Takao Shimayoshi, Ayako Takeuchi
The 9th Word Congress of Biomechanics 2022.7.14
-
Contributions of NCLX and NCX to mitochondrial Na+-Ca2+ exchange in mouse brain
Ayako Takeuchi, Satoshi Matsuoka
The 98th Annual Meeting of the Physiological Society of Japan 2021.3.29
-
A simulation analysis of Na+ and Ca2+ dynamics in cardiomyocyte during ischemia and reperfusion
Satoshi Matsuoka, Takao Shimayoshi, Ayako Takeuchi
2022.3
-
新規Cl-チャネルTMC4の味細胞活動電位における役割に関する数理モデル解析 Invited
竹内綾子
日本農芸化学会 2022年度大会 2022.3
-
A simulation study of cardiac ischemia and reperfusion
Satoshi Matsuoka, Takao Shimayoshi, Ayako Takeuchi
2021 Cardiac Physiome Workshop 2021.11
-
心筋虚血・再灌流の数理モデル解析
松岡達, 嶋吉隆夫, 竹内綾子
第66回中部日本生理学会 2021.10
-
Characteristics of Ca2+ efflux from mitochondria Invited
Ayako Takeuchi, Mohammed Moinul Islam, Satoshi Matsuoka
2020.3
-
Electrophysiological measurement of mitochondrial Na+-Ca2+ exchange in mouse heart
Mohammed Moinul Islam, Ayako Takeuchi, Satoshi Matsuoka
64th Biophysical meeting 2020.2
-
Property and roles of mitochondrial Na+-Ca2+ exchange in heart Invited
Satoshi Matsuoka, Mohammed M. Islam, Yukari Takeda, Ayako Takeuchi
The 50th NIPS international symposium「MIRACLES」In Cardiovascular Physiology～Metabolism, Interactions, Regulation, Application, Chemical Biology, Longevity, Exercise and Signaling～ 2019.12
-
Electrogenicity of mitochondrial Na+-Ca2+ exchange in mouse heart
2019.10
-
脳ミトコンドリアからのCa2+排出におけるNCLXおよびNCXの寄与
竹内綾子, 松岡達
第66回中部日本生理学会 2019.10
-
脳ミトコンドリアからのCa2+排出メカニズム
竹内綾子, 松岡達
第4回イオンチャネル研究会～チャネル花笠～ 2019.8
-
Evaluation of effects of empagliflozin on mouse ventricular myocytes
Hinako Suzuki, Takuma Yoshizawa, Shunsuke Aoki, Saki Watanabe, Yukari Takeda, Ayako Takeuchi, Satoshi Matsuoka
9th FAOPS congress 2019.3
-
Roles of mitochondrial Ca2+ channels/transporters in cellular functions Invited
Ayako Takeuchi, Satoshi Matsuoka
The 49th NIPS International Symposium Ion channels: looking back, seeing ahead 2018.12
-
マウス洞房結節細胞のlocal Ca releaseに対するミトコンドリアNa/Ca交換の関与
竹田有加里, 竹内綾子, 松岡達
日本生理学雑誌(Web) 2018.11
-
ミトコンドリアNa+-Ca2+交換の電気生理学的測定
モハメド・モイヌル・イスラム, 竹内綾子, 松岡達
生理学研究所研究会 2018.11
-
Intracellular localization of mitochondrial Na+-Ca2+ exchanger NCLX in mice ventricular myocytes
Ayako Takeuchi, Satoshi Matsuoka
62nd Biophysical Meeting 2018.2
-
Dysregulation of a potassium channel, THIK-1, targeted by the caspase accelerates cell shrinkage during apoptosis
Kazuhiro Sakamaki, Toshiya Sakata, Ayako Takeuchi, Chiyo Takagi, Hajime Shinoda, Akiko Saito, Takeharu Nagai, Satoshi Matsuoka, Naoto Ueno
2017.12
-
シングルファイバーを用いた神経膠芽腫細胞遊走におけるミトコンドリア動態の解析
河合佑介, 竹内綾子, 松岡達, 藤田聡
日本バイオマテリアル学会大会予稿集(Web) 2017.11.13
-
Frequency-dependences of action potential and Ca2+ transient and roles of mitochondrial Na+/Ca2+ exchange in mice ventricular myocyte International conference
Yukari Takeda, Misaki Tsukioka, Shino Fujisawa, Moe Fujisawa, Yousuke Shimizu, Erika Iwai, Rena Horie, Saki Matsunaka, Ayako Takeuchi, Satoshi Matsuoka
2017 Cardiac Physiome Workshop 2017.11
-
TAKEUCHI Ayako, KIM Bongju, MATSUOKA Satoshi
2017.3
-
MURATA Takuya, TAKEUCHI Ayako, MATSUOKA Satoshi
第94回日本生理学会大会 2017.3
-
MATSUOKA Satoshi, TAKEUCHI Ayako, SAITO Ryuta, HIMENO Yukiko
2017.3
-
神経膠芽腫細胞遊走におけるミトコンドリア動態のシングルファイバーを用いた解析
河合佑介, 竹内綾子, 藤田聡, 松岡達
日本生理学雑誌(Web) 2017.2
-
アポトーシスにおける細胞収縮に関わるカリウムチャネルTHIK‐1の同定とその作用機序の解明
SAKAMAKI Kazuhiro, SAKATA Toshiya, TAKEUCHI Ayako, TAKAGI Chiyo, SHINODA Hajime, SAITO Akiko, NAGAI Takeharu, MATSUOKA Satoshi, UENO Naoto
日本生化学会大会(Web) 2017
-
ミトコンドリア‐小胞体Ca2+クロストークに関するフィジオーム研究 Invited
竹内綾子, 松岡達
2016.5
-
TAKEUCHI Ayako, MATSUOKA Satoshi
2016.3
-
ミトコンドリアNa+‐Ca2+交換輸送体NCLXによるBリンパ球細胞走化の調節
松岡達, 金鳳柱, 竹内綾子
2014.11
-
マウス洞房結節細胞におけるミトコンドリア―筋小胞体の構造的・機能的クロストーク解析
竹内綾子, 松岡達
2014.11
-
ミトコンドリアNa‐Ca交換輸送体NCLXを介した心筋細胞自動能制御
竹内綾子, 金鳳柱, 松岡達
2012.9.10
-
Involvements of Ca transporters and channels in the cardiac cell volume regulation
Takeuchi Ayako, Sarai Nobuaki, Matsuoka Satoshi, Noma Akinori
日本生理学会大会発表要旨集 2007.3
-
Quantitative analysis of cardiac cell volume regulation by experiments and simulation
Takeuchi Ayako, Tatsumi Shuji, Sarai Nobuaki, Terashima Keisuke, Matsuoka Satoshi, Noma Akinori
日本生理学会大会発表要旨集 2006.3
-
心虚血再潅流傷害に対するループ利尿薬の効果~細胞モデルを用いた考察~
竹内綾子, 松岡達, 野間昭典, 乾賢一
2004.9
-
薬剤性腎障害からの回復過程における尿細管薬物トランスポータ群の発現変動
竹内綾子, 道下孝恒, 紀琳, 増田智先, 奥田真弘, 乾賢一
日本腎臓学会誌 2003.4.25
-
バンコマイシン誘発急性腎障害からの回復過程における有機イオントランスポータ群の発現変動
竹内綾子, 道下孝恒, 増田智先, 奥田真弘, 乾賢一
薬剤学 2003.3.5
-
新規Na+依存性グルコーストランスポータのcDNAクローニングと機能解析
堀場直, 竹内大輔, 竹内綾子, 増田智先, 奥田真弘, 乾賢一
日本薬学会年会要旨集 2003.3.5
-
腎尿細管PGE2輸送及び産生制御における有機アニオントランスポータOAT‐Kの役割
清水百合子, 増田智先, 竹内綾子, 斎藤秀之, 乾賢一
日本腎臓学会誌 2002.4.25
-
堀場直, 増田智先, 竹内綾子, 斎藤秀之, 乾賢一
日本腎臓学会誌 2002.4.25
-
高尿酸血症モデルラットにおける腎尿細管薬物輸送活性と有機イオントランスポータの発現量変動
土生康司, 矢野育子, 竹内綾子, 斎藤秀之, 乾賢一
日本薬学会年会要旨集 2002.3.5
-
腎局在性有機アニオントランスポータOAT‐K1及びOAT‐K2の多選択的基質認識特性
竹内綾子, 増田智先, 上井優一, 斎藤秀之, 乾賢一
日本薬学会年会要旨集 2002.3.5
-
竹内綾子, 増田智先, 斎藤秀之, 乾賢一
薬物動態 2001.4.28
-
腎局在性有機アニオントランスポータOAT‐K1及びOAT‐K2の基質認識特性
竹内綾子, 増田智先, 斎藤秀之, 乾賢一
日本腎臓学会誌 2001.4.25
-
竹内綾子, 増田智先, 斎藤秀之, 乾賢一
薬物動態 2000.9.15
-
5/6腎摘出ラットにおける尿細管有機アニオントランスポータOAT‐K1及びOAT‐K2の発現変動
竹内綾子, 増田智先, 斎藤秀之, 橋本征也, 乾賢一, 土井俊夫
日本腎臓学会誌 2000.4.25
-
腎局在性有機アニオントランスポータOAT‐Kの細胞膜発現と薬物認識
増田智先, 竹内綾子, 斎藤秀之, 橋本征也, 乾賢一
膜シンポジウム 1998.11
-
腎局在性有機アニオントランスポータOAT‐K1及びOAT‐K2の構造・機能解析
増田智先, 竹内綾子, 茨本浩嗣, 斎藤秀之, 橋本征也, 乾賢一
日本膜学会年会講演要旨集 1998.5
-
茨本浩嗣, 竹内綾子, 増田智先, 斎藤秀之, 橋本征也, 乾賢一
日本薬学会年会要旨集 1998.3
Awards
-
2021年度日本生理学会 入澤宏・彩記念JPS優秀論文賞、2021年度 第15回 細胞と分子生理/上皮膜研究グループ J.P.S.優秀論文賞
2022.3
Kasahara Y, Narukawa M, Ishimaru Y, Kanda S, Umatani C, Takayama Y, Tominaga M, Oka Y, Kondo K, Kondo T, Takeuchi A, Misaka T, Abe K, Asakura T. TMC4 is a novel chloride channel involved in high-concentration salt taste sensation. J Physiol Sci, 71, 23, 2021
-
2020年度日本生理学会 入澤宏・彩記念JPS優秀論文賞
2021.3
Islam MM, Takeuchi A, Matsuoka S. Membrane current evoked, by mitochondrial Na+-Ca2+ exchange in mouse heart. J Physiol Sci, 70, 24, 2020
-
令和2年度 福井大学医学系部門長奨励賞
2020.10
竹内綾子
-
福井大学研究者奨励賞（男女共同参画）
2017.3
竹内 綾子
-
平成25年度 入澤宏・彩記念若手研究奨励賞 [心臓・循環分野]
2014.3
竹内 綾子
-
第90回日本生理学会大会 佐川喜一賞
2013.3
竹内 綾子
-
Cardiac Physiome Workshop 2012 Poster Prize Winner
2012.10
TAKEUCHI Ayako
-
第11回日本生理学会奨励賞
2010.5
竹内 綾子
-
第一回トランスポーター研究会 優秀発表賞
2006.12
竹内 綾子
Research Projects
-
組織特異的なミトコンドリアCa2+動態の統合的解明
2022.07 - 2023.02
令和4年度 福井大学研究推進支援（次世代卓越研究者に対する支援）
竹内綾子
Grant amount：\700000
-
ミトコンドリアCa2+動態を起点とした神経細胞機能制御の分子機序解明
Grant number：22K06841 2022.04 - 2025.03
日本学術振興会 科学研究費助成事業 基盤研究(C) 基盤研究(C)
竹内 綾子
Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）
-
Decoding molecular orchestration of dopaminergic neuronal cell death by a combination of physiological experiments and computational modelling
2022.03 - 2023.03
公益財団法人 日立財団 2021年度（第53回） 倉田奨励金
竹内綾子
Authorship：Principal investigator
-
development of a method to analyze local organelle function in situ
Grant number：19K22509 2019.06 - 2022.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Challenging Research (Exploratory) Challenging Research (Exploratory)
Matsuoka Satoshi
Grant amount：\6240000 （ Direct expense: \4800000 、 Indirect expense：\1440000 ）
There is no way to measure directly mitochondrial membrane potential in living cells. We aimed to develop a new micropipette method to measure directly mitochondrial membrane potential. After the improvement of experimental equipment, selection of proper glass capillary, adjustment of puller and selection of proper mitochondria-specific fluorescence dye, we tried direct measurement of mitochondrial membrane potential in living cardiomyocytes with microelectrodes. However, a large negative membrane potential corresponding to mitochondrial membrane potential could not be detected. The possible reasons are damage and depolarization of mitochondria by the microelectrodes, or non-penetration of microelectrodes through mitochondrial inner/outer membrane. It seems, however, possible to measure directly mitochondrial membrane potential with cells having giant mitochondria.
-
Elucidation of metabolism-excitation-contraction coupling in cardiomyocytes through metabolic imaging
Grant number：19H03400 2019.04 - 2022.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
Matsuoka Satoshi
Grant amount：\17550000 （ Direct expense: \13500000 、 Indirect expense：\4050000 ）
We succeeded in recording membrane current generated by mitochondrial Na+-Ca2+ exchange for the first time, and demonstrated that mitochondrial Na+-Ca2+ exchange is electrogenic and voltage-dependent. We demonstrated that a part of Ca2+ transported by mitochondrial Na+-Ca2+ exchange to the outside of mitochondria enters sarcoplasmic reticulum, then affects Ca2+ release from sarcoplasmic reticulum and frequency of the action potential generation of sinoatrial node cells (automaticity). We developed a new mathematical model of cardiomyocyte including H+ flux across mitochondria and intracellular pH regulation.
-
Bリンパ球機能制御を司るミトコンドリア－小胞体連関の可視化
2018.11 - 2019.11
公益財団法人 住友財団 2018年度基礎科学研究助成
竹内 綾子
Authorship：Principal investigator Grant type：Competitive
-
Physiological role of mitochondrial heterogeneity in ventricular myocytes
Grant number：18K06869 2018.04 - 2021.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
Takeuchi Ayako
Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）
The purpose of the study was to clarify physiological roles of functional heterogeneity of mitochondria in ventricular myocytes. We obtained following results. 1. mitochondrial Na-Ca exchanger (NCLX) was localized near sarcoplasmic reticulum SERCA2>sarcoplasmic reticulum RyR>sarcolemmal Na-K ATPase, 2. NCLX was electrogenic, and reverse mode of Na-Ca exchange activity was much slower than forward mode, 3. mitochondrial membrane was more depolarized and response to uncoupler FCCP was slower at cellular edge than those at central part. Then we constructed a new mathematical model of ventricular myocyte which can calculate pH and mitochondrial ion dynamics, to analyze mechanisms explaining experimental data.
-
新規免疫制御薬の創製を目指したリンパ球特異的ミトコンドリアCa2+トランスポートソームの解明
2017.11 - 2018.12
公益財団法人 持田記念医学薬学振興財団 平成29年度 研究助成金
竹内 綾子
Authorship：Principal investigator Grant type：Competitive
-
Bリンパ球ミトコンドリアCa2+動態を介する新たな免疫応答制御
2017.11
公益財団法人 武田科学技術振興財団 医学系研究奨励
竹内 綾子
Authorship：Principal investigator Grant type：Competitive
-
神経膠芽腫細胞におけるミトコンドリア－細胞遊走・走化連関に関する研究
2017.09 - 2018.03
福井大学生命センター学内共同研究等
竹内 綾子, 藤田 聡
Authorship：Principal investigator Grant type：Competitive
-
Bリンパ球ミトコンドリアCa2+トランスポートソームを標的とした新たな免疫制御
2017.08 - 2018.03
平成29年度 福井大学研究推進支援（学術研究育成支援）
竹内 綾子
Authorship：Principal investigator Grant type：Competitive
-
新規Cl輸送体によるClダイナミクス‐ミトコンドリアとBリンパ球の機能連関の制御メカニズムの解明
2016.04 - 2017.03
2016年度稲盛財団研究助成
竹内 綾子
Authorship：Principal investigator Grant type：Competitive
-
Bリンパ球細胞機能を制御する新規Cl-輸送体の同定
2015.09 - 2016.03
福井大学生命センター学内共同研究等（萌芽的・先進的研究）
竹内 綾子
Authorship：Principal investigator Grant type：Competitive
-
Study on regulation mechanisms of cardiac rhythm and energy metabolism via mitochondria-sarcoplasmic reticulum coupling
Grant number：15H04674 2015.04 - 2018.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
Matsuoka Satoshi, Takeuchi Ayako
Grant amount：\17290000 （ Direct expense: \13300000 、 Indirect expense：\3990000 ）
NCLX-knockout mice were created using the CRISPR-Cas9 method. Some of the homo-knockout mice show phenotypes different form wild type mice, such as low body weight, and abnormalities of heart and kidney. The Langendorff perfusion of mouse heart with a NCLX blocker (CGP-37157) tended to have decreased heart rate. In isolated mouse ventricular myocytes, CGP-37157 prolonged the 30 and 50% duration of action potential, and augmented the amplitude of Ca2+ transient probably due to the increase of SR Ca2+ content. A new comprehensive mathematical model of cardiac mitochondria was developed and published. A new mathematical model of sinoatrial cell, which contains the Ca2+ interaction between mitochondria and SR, was developed.
-
How does the nematode find its host? -Optogenetics-based approach to the nervous-behavior system
Grant number：15K14896 2015.04 - 2017.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
Takeuchi-Kaneko Yuko, TAKEUCHI Ayako, OKUMURA Etsuko
Grant amount：\3900000 （ Direct expense: \3000000 、 Indirect expense：\900000 ）
An entomophilic nematode Caenorhabditis japonica has a species-specific relationship with its carrier bug Parastrachia japonensis. We hypothesized that this relationship is based on a chemical communication via semiochemical and conducted several experiments to clarify the mechanism in detail.
Results obtained in preference tests showed that C. japonica uses semiochemical(s) contained in hexane extract of the host insect for host recognition, of which list has been narrowed by GC-MS analysis. Also, C. japonica was strongly attracted to benzaldehyde, which is known as one of the attractants for C. elegans. This suggests that C. japonica may equip and utilize a neural network similar to that of C. elegans. -
Study on the mitochondria-sarcoplasmic reticulum 3D Ca crosstalk in cardiomyocytes
Grant number：26291019 2014.04 - 2017.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
Takeuchi Ayako, Amano Akira
Grant amount：\16770000 （ Direct expense: \12900000 、 Indirect expense：\3870000 ）
The purpose of the study was to clarify physiological roles of mitochondria-sarcoplasmic reticulum 3D Ca crosstalk in cardiomyocytes. From combination study of experiments and mathematical simulations, we obtained following results. 1. Parameters explaining mitochondria-sarcoplasmic reticulum localization were obtained by analyzing electron microscopy data on mouse cardiomyocytes. 2. In vitro localization analyses were performed using HEK293 cells and mouse cardiomyocytes and it was suggested that mitochondrial Na/Ca exchanger NCLX and sarcoplasmic reticulum Ca pump SERCA were localized in close proximity to each other. 3. A mathematical model of a detailed mitochondrial oxidative phosphorylation was newly constructed. The model predicted the contribution of Ca-dependent regulations of mitochondrial energy metabolism with various compositions of energy substrates. In addition, the roles of mitochondria-sarcoplasmic reticulum crosstalk were also analyzed.
-
ミトコンドリアによる心自動能制御メカニズムの多階層解析
Grant number：25136707 2013.04 - 2015.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area) Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
竹内 綾子
Grant amount：\10400000 （ Direct expense: \8000000 、 Indirect expense：\2400000 ）
ミトコンドリアを介した洞房結節自動能制御のメカニズムを明らかにすることを目的として、平成26年度は以下の検討を行った。
単離した洞房結節を用いて、洞房結節細胞の電子顕微鏡像を取得した。その結果、ミトコンドリアと筋小胞体の面積比はそれぞれ約15%、4%であった。また、ほぼ全てのミトコンドリアが筋小胞体と近接していた。一方、筋小胞体の約35%がミトコンドリアと近接していた。さらに、3D-SEMを用いて洞房結節細胞の三次元立体構築を行い、洞房結節細胞においてはT管がほとんど発達していないことを確認した。
上記実験データをもとに、ミトコンドリアと筋小胞体の面積比、両オルガネラの近接する割合などを、前年度構築した2種類の簡易洞房結節細胞モデルに導入し、精緻化した。シミュレーション解析から、ミトコンドリアNa-Ca交換輸送体NCLXの自動能発生における寄与を調べた。その結果、Caクロックで駆動されるモデルではNCLXはリズムを促進したのに対し、膜クロックで駆動されるモデルではNCLXの効果がなかった。Caクロックで駆動されるモデルでは、細胞膜直下のsubsarcolemmal spaceに全ての筋小胞体が局在すると仮定している。洞房結節ではT管がほとんど発達していないことを考え合わせると、実際の洞房結節細胞ではミトコンドリアNCLXのリズム発生における寄与はほとんどないと考えられた。
以上の成果を学会発表するとともに、総説として論文発表した。 -
Pacemaking mechanism of human SA node cell using human iPS-derived cardiomyocytes
Grant number：24650260 2012.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
TAKEUCHI Ayako
Grant amount：\3900000 （ Direct expense: \3000000 、 Indirect expense：\900000 ）
The purpose of the present study was to clarify pacemaking mechanisms of human cardiac pacemaker cells, SA node cells. In order to achieve the goals, I performed cellular physiological experiments using human iPS-derived cardiomyocytes and mathematical simulations. Several combinations of chemicals enhanced proliferation of human iPS-derived cardiomyocytes, with similar electrophysiological characteristics. Theoretical analyses suggested that coupling of mitochondrial and sarcoplasmic reticulum Ca dynamics is important for pacemaking, and that contribution of mitochondrial Ca transporter is mechanism dependent.
-
Controlling cellular function via modulating cytosolic chloride dynamics
Grant number：23689011 2011.11 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A) Grant-in-Aid for Young Scientists (A)
TAKEUCHI Ayako
Grant amount：\15080000 （ Direct expense: \11600000 、 Indirect expense：\3480000 ）
The purpose of the present study was to clarify the mechanisms and significances of "cellular Cl-Ca dynamics coupling". To achieve the goals, I picked up two kinds of cells, cardiomyocytes and lymphocytes as typical excitable and non-excitable cells, respectively, and performed a combination study of cellular physiological experiments and mathematical simulations. As a result, I obtained following achievements. 1. There is an intracellular Cl store which is involved in the cellular Cl dynamics. 2. "Cellular Cl-Ca dynamics coupling" do exist. 3. Mitochondria are major organelle which participate in the "cellular Cl-Ca dynamics coupling".
-
Study on structure and function of mitochondria Na-Ca exchange(NCLX)
Grant number：23390042 2011.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
MATSUOKA Satoshi, TAKEUCHI Ayako, KIM Bongju
Grant amount：\19760000 （ Direct expense: \15200000 、 Indirect expense：\4560000 ）
In B lymphocyte cell lines (A20 and DT 40), it was demonstrated that mitochondrial Na/Ca exchanger (NCLX) is associated with mitochondrial Ca extrusion, modulation of endoplasmic reticulum Ca content, endoplasmic reticulum Ca release upon BCR-stimulation, store-operated Ca entry and chemotaxis. In cardiomyocyte cell line (HL-1), it was also demonstrated NCLX extrudes mitochondrial Ca and modulates sarcoplasmic reticulum Ca content. Additionally, it was found that NCLX modulates spontaneous beating frequency. These results were well reproduced by mathematical models of B lymphocyte, HL-1 cell and sinoatrial node cell. Taken together, it was suggested that NCLX act as a Ca provider from mitochondria to sarco- and endo-plasmic reticulum.
-
Predicting the fate of lymphocytes by the initial Ca response pattern
Grant number：23650258 2011 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
MATSUOKA Satoshi, TAKEUCHI Ayako, KIM Bongju
Grant amount：\3640000 （ Direct expense: \2800000 、 Indirect expense：\840000 ）
Lymphocyte cell lines (A20 B cells, etc.) and mouse spleen B lymphocytes were used for analyses. These cells were loaded with Ca2+fluorescent indicators (Fluo-4, etc.). Cytoplasmic Ca2+responses to the stimulation of surface antigen receptors were recorded from individual cells using a fluorescence microscope and the data were collected to make a database. Additionally, systems were developed to detect cell death, apoptosis and mitochondrial membrane potential from individual cells. Statistical analysis and correlational analysis were performed using these digitalized data.
-
ミトコンドリアクロックを介した心拍動リズム制御の分子機構解析
2011
京都大学若手研究者ステップアップ研究費
竹内 綾子
Authorship：Principal investigator Grant type：Competitive
-
Chloride dynamics in beating cardiomyocytes
Grant number：21790200 2009 - 2010
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Grant-in-Aid for Young Scientists (B)
TAKEUCHI Ayako
Authorship：Principal investigator Grant type：Competitive
Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）
The purpose of the present study was to clarify the mechanisms and significance of Cl^-dynamics via intracellular organelle membranes in beating cardiomyocytes. To achieve these goals, cell physiological experiments in combination with computer simulation were performed and the following results were obtained. 1. Technique to measure the intracellular Cl^- dynamics was established. 2. Expression of CLIC2, an intracellular chloride channel, was analyzed in cell line of beating cardiomyocytes. 3. A comprehensive cardiomyocyte model was updated by incorporating pH homeostasis and detailed mitochondria to analyze dynamics of ions and energy substrates across the intracellular organelle membranes.
-
Studies on regulation of matrix ion dynamics and energy metabolism by mitochondria NCX
Grant number：20390057 2008 - 2010
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
MATSUOKA Satoshi, KIM Bongju, TAKATSUKA Kenji, TAKEUCHI Ayako
Grant amount：\19630000 （ Direct expense: \15100000 、 Indirect expense：\4530000 ）
The aim of this study was quantitative elucidation of physiological function of mitochondria. Mitochondrial and cytoplasmic Ca dynamics were studied by using Ca-sensitive fluorescent dyes in cardiac myocytes. Based on these data and previously published data, a mathematical model of mitochondria which can well reproduce mitochondrial Ca, Na and H changes was newly developed. A comprehensive mitochondria model was accomplished by integrating the model with the metabolic model including oxidative phosphorylation and TCA cycle. It was suggested that Ca- and phosphate-dependent regulatory processes are important in keeping the balance of energy metabolites.
-
心筋細胞クロライドダイナミクスと興奮―収縮連関
Grant number：19790164 2007
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Grant-in-Aid for Young Scientists (B)
竹内 綾子
Grant amount：\1600000 （ Direct expense: \1600000 ）
-
臓器特異的上皮細胞モデルを用いた薬物体内動態の予測法の開発に関する研究
Grant number：17790120 2005 - 2006
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Grant-in-Aid for Young Scientists (B)
竹内 綾子
Grant amount：\3600000 （ Direct expense: \3600000 ）
小腸や腎臓などの上皮細胞では種々チャネルやトランスポータを介した様々な生理物質の輸送が行われており、生体の恒常性維持に重要な役割を果たしている。本研究では、生体側のダイナミックな生理機能の変化を再現し、それに応じた薬物体内動態変動を予測することを目的とした。平成17年度には包括的上皮細胞モデルのプロトタイプの作成を行った。また、多くの動物細胞に共通の一般的な生理機能である細胞容積調節機構に対する種々トランスポータ、チャネルの寄与を予測した。平成18年度は、上記研究成果を発展させ実験的にモデルの妥当性、定量性を検証し、その結果をモデルに還元し精緻化することによって、コンピュータ上におけるダイナミックな生理機能変化の再現を実現させた。
細胞モデルを用いた解析によって作業仮説をたて、実験的に種々パラメータ(細胞の膜電位、イオン濃度(Na^+,Ca^<2+>,Cl^-)並びに容積)を測定し仮説を検証するという「モデル予測-実験検証」のサイクルを繰り返すことによって、従来その関与が明らかでなかったCa^<2+>担体の細胞容積調節における役割を明らかにすることができた。すなわち、Na^+/K^+ pumpは生体の恒常性維持に重要な役割を果たすが、これが阻害されるという病的な状態においても、細胞膜Ca^<2+>ポンプとNa^+/Ca^<2+>交換機転との協調作用によって、ある程度細胞容積が維持されるという代償機構の存在を実験的に証明することができた。また、細胞内Ca^<2+>濃度の変化はタンパク質分解酵素の活性化など細胞のviabilityと密接な関係があることが従来知られていたが、細胞膜イオン透過性にも大きく影響を与え、その結果細胞容積調節機構において主要な因子となりうることを新たに明らかにした。これらの成果をモデルに還元し、薬物添加時における細胞応答を多岐にわたるパラメータについて定量的に予測することに成功した。 -
薬物腎排泄に関わる有機アニオントランスポータの分子的多様性と機能解析に関する研究
Grant number：02J01530 2002 - 2003
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows Grant-in-Aid for JSPS Fellows
竹内 綾子
Grant amount：\2500000 （ Direct expense: \2500000 ）
尿細管上皮細胞に発現する薬物トランスポータ群は、異物や代謝老廃物の解毒機構として重要な役割を担っている。本研究では、薬物トランスポータ群の生理的・薬物動態学的役割を解明するため、種々疾患モデル動物を用いて病態時におけるトランスポータの発現変動と薬物体内動態の変化との関連について精査した。また、ヒト型薬物トランスポータの遺伝子多型による機能変化についても検討を行った。
高尿酸血症モデルラット並びにバンコマイシン誘発急性腎障害ラットを用いて、有機アニオントランスポータ(rOAT1及びrOAT3)及び有機カチオントランスポータ(rOCT1及びrOCT2)の発現変動を調べた。その結果、いずれのモデルでもrOAT1及びrOAT3の発現量が著しく低下することが判明した。さらに、有機アニオントランスポータの典型的基質であるp-アミノ馬尿酸やメトトレキサートの腎クリアランスはこれらトランスポータの発現と対応した変動を示すことが明らかとなった。一方、バンコマイシン誘発急性腎障害ラットではrOCT1及びrOCT2いずれの発現量も大きく変動しなかったのに対し、高尿酸血症モデルラットではrOCT2発現量の著しい低下と、カチオン性薬物であるシメチジンの腎クリアランスの低下が観察された。従って、疾患時における薬物トランスポータ群の発現変動は、基質となる薬物の体内動態に大きく影響を与えることが示唆された。
腎不全時における薬物トランスポータ群の役割を総合的に理解するために、慢性腎不全モデルラットと正常ラットを用いて発現遺伝子のin silicoサブトラクションを行った。その結果、成長因子関連遺伝子や細胞骨格遺伝子などの発現頻度は慢性腎不全群で増加するのに対し、トランスポータ関連遺伝子の発現頻度は減少することが判明した。
ヒト有機カチオントランスポータhOCT1の新規一塩基多型について、in vitro発現系を用いて機能解析を行った結果、正常な発現にも拘らず著しく機能低下を伴うことを見出した。
Class subject in charge
-
Introduction to Communication for Pharmaceutical Sciences （2025academic year） 1st semester - 火3～4
-
Introduction to Communication for Pharmaceutical Sciences （2025academic year） 1st semester - 火3～4
-
Analytical Sciences and Physical Chemistry （2025academic year） special - その他
-
Physiology （2025academic year） 1st and 2nd semester - 水5～6
-
Physiology （2025academic year） 1st and 2nd semester - 水5～6
-
Physiology 1 （2025academic year） 1st semester - 水5～6
-
Physiology 1 （2025academic year） 1st semester - 水5～6
-
Physiology 2 （2025academic year） Second semester - 水5～6
-
Physiology 2 （2025academic year） Second semester - 水5～6