信州大学HOMEENGLISH交通・キャンパス案内

研究者総覧研究者総覧

研究者、研究内容などで検索
項目別検索はこちら

山田 充彦  ヤマダ ミツヒコ

教員組織学術研究院(医学系)電話番号
教育組織医学部 医学科 分子薬理学FAX番号
職名教授メールアドレスmyamada@shinshu-u.ac.jp
住所〒390-8621 長野県松本市旭3-1-1ホームページURLhttp://www.shinshu-u.ac.jp/faculty/medicine/chair/i-yakuri/index.html

更新日:2023/07/20

プロフィール

研究分野
薬理学一般
循環器内科学
神経生理学・神経科学一般
生理学一般
胎児医学、小児成育学
キーワード:心臓 , イオンチャネル , 細胞内カルシウム代謝 , 興奮収縮連関 , G蛋白質共役型受容体 , 細胞内情報伝達系 , 薬力学 , 小児心不全 , 後腎分化 , 創薬研究
現在の研究課題
心筋L型カルシウムチャネルの生理学的、病態生理学的、薬理学的解析
キーワード:心臓 , L型カルシウムチャネル , 心不全 , 不整脈 , 作用薬・阻害薬
小児心不全治療薬の開発

後腎分化機構の研究

所属学会
所属学会
米国生理学会
米国生物物理学会
日本生理学会
日本循環器学会
日本心電学会

所属学会役職担当
日本薬理学会 , 代議員
学歴
出身学校・専攻等(大学院を除く)
1984 , 神戸大学 , 医学部 , 医学科

取得学位
医学博士

免許・資格等
19840528 , 医師免許
受賞学術賞
2005 , 第5回医科学応用研究財団助成による日本心電学会論文賞
1993 , 財団法人循環器学研究振興財団内田賞
研究職歴等
研究職歴
2004- , 信州大学医学部分子薬理学講座教授
2002-2004 , 大阪大学大学院医学系研究科 情報薬理学講座 助教授
1998-2002 , 国立循環器病センター研究所心臓生理部、神経性調節研究室長
1994-1998 , 大阪大学医学部第二薬理学講座助手

研究職歴以外の職歴
1991-1992 , 兵庫病院内科医師
1990-1991 , 佐用共立病院内科医師
1989-1990 , 兵庫病院内科医師
1987-1989 , 医員
1984-1987 , 医員(研修医)

留学歴
1992-1994 , メイヨークリニック内科心・血管病部門ポストドクタルフェロー

研究活動業績

研究業績(著書・
発表論文等)
書籍等出版物
新しい小児心不全治療薬の開発をめざして, 熱血 循環器学 洋學社 井上信孝編集 , 1-15
洋學社 2019
Author:山田充彦


ヌクレオチドと薬物による心血管系ATP感受性K+チャネル活性化の分子機構, 倉智 嘉久編:別冊・医学のあゆみイオンチャネル最前線update , pp 101-107
医歯薬出版株式会社,東京 2005
Author:山田充彦


論文
新生児マウス心臓の機能的発達におけるサイトカイン受容体gp130の役割
信州医学雑誌,70(6):373-382 2022(Dec. 10)
Author:川岸 裕幸;山田 充彦


A reconstituted depolarization-induced Ca2+ release platform for validation of skeletal muscle disease mutations and drug discovery.
J Gen Physiol.,154(12):e202213230 2022(Nov.)
Author:Murayama T, Kurebayashi N, Numaga-Tomita T, Kobayashi T, Okazaki S, Yamashiro K, Nakada T, Mori S, Ishida R, Kagechika H, Yamada M, Sakurai T.
Abstract:In skeletal muscle excitation-contraction (E-C) coupling, depolarization of the plasma membrane triggers Ca2+ release from the sarcoplasmic reticulum (SR), referred to as depolarization-induced Ca2+ release (DICR). DICR occurs through the type 1 ryanodine receptor (RyR1), which physically interacts with the dihydropyridine receptor Cav1.1 subunit in specific machinery formed with additional essential components including β1a, Stac3 adaptor protein, and junctophilins. Exome sequencing has accelerated the discovery of many novel mutations in genes encoding DICR machinery in various skeletal muscle diseases. However, functional validation is time-consuming because it must be performed in a skeletal muscle environment. In this study, we established a platform of the reconstituted DICR in HEK293 cells. The essential components were effectively transduced into HEK293 cells expressing RyR1 using baculovirus vectors, and Ca2+ release was quantitatively measured with R-CEPIA1er, a fluorescent ER Ca2+ indicator, without contaminant of extracellular Ca2+ influx. In these cells, [K+]-dependent Ca2+ release was triggered by chemical depolarization with the aid of inward rectifying potassium channel, indicating a successful reconstitution of DICR. Using the platform, we evaluated several Cav1.1 mutations that are implicated in malignant hyperthermia and myopathy. We also tested several RyR1 inhibitors; whereas dantrolene and Cpd1 inhibited DICR, procaine had no effect. Furthermore, twitch potentiators such as perchlorate and thiocyanate shifted the voltage dependence of DICR to more negative potentials without affecting Ca2+-induced Ca2+ release. These results well reproduced the findings with the muscle fibers and the cultured myotubes. Since the procedure is simple and reproducible, the reconstituted DICR platform will be highly useful for the validation of mutations and drug discovery for skeletal muscle diseases.


小児期特有のアンジオテンシンシグナルと、その小児心不全治療への応用
Cardiac Practice,32:128-133 2022
Author:山田充彦


Cytokine receptor gp130 promotes postnatal proliferation of cardiomyocytes required for the normal functional development of the heart.
Am J Physiol Heart Circ Physiol.,323:H103-H120 2022
Author:Kawagishi H, Nakada T, Numaga-Tomita T, Larranaga M, Guo A, Song LS, Yamada M.


NRSF-GNAO1 Pathway Contributes to the Regulation of Cardiac Ca2+ Homeostasis.
Circ Res.,130:234-248 2022
Author:Inazumi H, Kuwahara K, Nakagawa Y, Kuwabara Y, Numaga-Tomita T, Kashihara T, Nakada T, Kurebayashi N, Oya M, Nonaka M, Sugihara M, Kinoshita H, Moriuchi K, Yanagisawa H, Nishikimi T, Motoki H, Yamada M, Morimoto S, Otsu K, Mortensen RM, Nakao K, Kimura T.


Adrenomedullin-RAMP2 and -RAMP3 Systems Regulate Cardiac Homeostasis during Cardiovascular Stress.
Endocrinology,162:bqab001 2021
Author:Cui N, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Tanaka M, Wei Y, Kakihara S, Zhao Y, Aruga K, Kawagishi H, Nakada T, Yamada M, Shindo T.


Beta-Arrestin-Biased AT1 Agonist TRV027 Causes a Neonatal-Specific Sustained Positive Inotropic Effect Without Increasing Heart Rate.
JACC Basic Transl Sci,5:1057-1069 2020
Author:Kashihara T, Kawagishi H, Nakada T, Numaga-Tomita T, Kadota S, Wolf EE, Du CK, Shiba Y, Morimoto S, Yamada M.


Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo.
Sci Rep.,10:11883 2020
Author:Ichimura H, Kadota S, Kashihara T, Yamada M, Ito K, Kobayashi H, Tanaka Y, Shiba N, Chuma S, Tohyama S, Seto T, Okada K, Kuwahara K, Shiba Y.


Prostanoid EP4 Receptor-Mediated Augmentation of Ih Currents in A beta Dorsal Root Ganglion Neurons Underlies Neuropathic Pain.
J Pharmacol Exp Ther.,368:50-58 2019
Author:Zhang H, Kashihara T, Nakada T, Tanaka S, Ishida K, Fuseya S, Kawagishi H, Kiyosawa K, Kawamata M, Yamada M.


Impact of chronic kidney dysfunction on serum Sulfatides and its metabolic pathway in mice.
Glycoconj J.,36:1-11 2019
Author:Yamada Y, Harada M, Hashimoto K, Guo R, Nakajima T, Kashihara T, Yamada M, Aoyama T, Kamijo Y.


Effects of hypertension and antihypertensive treatments on sulfatide levels in serum and its metabolism.
Hypertens Res,42:598-609 2019
Author:Guo R, Hu X, Yamada Y, Harada M, Nakajima T, Kashihara T, Yamada M, Aoyama T, Kamijo Y.


Physical interaction of junctophilin and the CaV1.1 C terminus is crucial for skeletal muscle contraction.
Proc Natl Acad Sci U S A.,115:4507-4512 2018
Author:Nakada T, Kashihara T, Komatsu M, Kojima K, Takeshita T, Yamada M.


Increase in phospholamban content in mouse skeletal muscle after denervation.
J Muscle Res Cell Motil.,39:163-173 2018
Author:Komatsu M, Nakada T, Kawagishi H, Kato H, Yamada M.


Sonic hedgehog signaling regulates the mammalian cardiac regenerative response.
J Mol Cell Cardiol.,123:180-184 2018
Author:Kawagishi H, Xiong J, Rovira, II, Pan H, Yan Y, Fleischmann BK, Yamada M, Finkel T.


PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus.
Pflugers Arch.,470:909-921 2018
Author:Guo X, Kashihara T, Nakada T, Aoyama T, Yamada M.


Angiotensin II activates CaV1.2 Ca2+ channels through beta-arrestin2 and casein kinase 2 in mouse immature cardiomyocytes.
J Physiol. (Lond.),595:4207-4225 2017
Author:Kashihara T, Nakada T, Kojima K, Takeshita T, Yamada M.


Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.
J Mol Cell Cardiol.,81:139-149 2015
Author:Gautam M, Fujita D, Kimura K, Ichikawa H, Izawa A, Hirose M, Kashihara T, Yamada M, Takahashi M, Ikeda U, Shiba Y.


Cardiac overexpression of constitutively active Galpha q Causes angiotensin II type1 receptor activation, leading to progressive heart failure and ventricular arrhythmias in transgenic mice.
PLoS One.,9:e106354 2014
Author:Matsushita N, Kashihara T, Shimojo H, Suzuki S, Nakada T, Takeishi Y, Mende U, Taira E, Yamada M, Sanbe A, Hirose M.


Beta2-Adrenergic and M2-muscarinic receptors decrease basal t-tubular L-type Ca2+ channel activity and suppress ventricular contractility in heart failure.
Eur J Pharmacol.,724:122-131 2014
Author:Kashihara T, Hirose M, Shimojo H, Nakada T, Gomi S, Hongo M, Yamada M.


Phlorizin prevents electrically-induced ventricular tachyarrhythmia during ischemia in Langendorff-perfused guinea-pig hearts.
Biol Pharm Bull.,37:1168-1176 2014
Author:Hirose M, Shibazaki T, Nakada T, Kashihara T, Yano S, Okamoto Y, Isaji M, Matsushita N, Taira E, Yamada M.


TRPM4 Channels Mediate Hypertonicity-induced, Ca2+-impermeable, Non-selective Cation Currents in a Cervical Cancer Cell Line, HeLa Cells.
Shinshu Med J.,62:33-44 2014
Author:Gomi S, Nakada T, Kashihara T, Ikeda U, Yamada M.


Novel regulation of cardiac metabolism and homeostasis by the adrenomedullin-receptor activity-modifying protein 2 system.
Hypertension. ,6:341-351 2013
Author:Yoshizawa T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Iesato Y, Koyama T, Uetake R, Yang L, Yamauchi A, Tanaka M, Toriyama Y, Igarashi K, Nakada T, Kashihara T, Yamada M, Kawakami H, Nakanishi H, Taguchi R, Nakanishi T, Akazawa H, Shindo T.


KGA-2727, a novel selective inhibitor of a high-affinity sodium glucose cotransporter (SGLT1), exhibits antidiabetic efficacy in rodent models.
J Pharmacol Exp Ther.,342:288-296 2012
Author:Shibazaki T, Tomae M, Ishikawa-Takemura Y, Fushimi N, Itoh F, Yamada M, Isaji M.


Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type Ca2+ channels revealed by Timothy syndrome mutation.
Eur J Pharmacol.,685:15-23 2012
Author:Sheng X, Nakada T, Kobayashi M, Kashihara T, Shibazaki T, Horiuchi-Hirose M, Gomi S, Hirose M, Aoyama T, Yamada M.


The proximal C-terminus of 1C subunits is necessary for junctional membrane targeting of cardiac L-type calcium channels.
Biochem J.,448:221-231 2012
Author:Nakada T, Flucher BE, Kashihara T, Sheng X, Shibazaki T, Horiuchi-Hirose M, Gomi S, Hirose M, Yamada M.


Chronic receptor-mediated activation of Gi/o proteins alters basal t-tubular and sarcolemmal L-type Ca2+ channel activity through phosphatases in heart failure.
Am J Physiol Heart Circ Physiol.,302:H1645-H1654 2012
Author:Kashihara T, Nakada T, Shimojo H, Horiuchi-Hirose M, Gomi S, Shibazaki T, Sheng X, Hirose M, Hongo M, Yamada M.


Nicorandil prevents Galphaq-induced progressive heart failure and ventricular arrhythmias in transgenic mice.
PLoS One.,7:e52667 2012
Author:Hirose M, Takeishi Y, Nakada T, Shimojo H, Kashihara T, Nishio A, Suzuki S, Mende U, Matsumoto K, Matsushita N, Taira E, Sato F, Yamada M.


Acid-sensing ion channels in blood volume regulation.
Circ J.,75:781-782 2011
Author:Yamada M.


Thrombin activates Ca2+-permeating nonselective cation channels through protein kinase C in human umbilical vein endothelial cells.
Shinshu Med J.,59:13-26 2011
Author:Tsujino N, Nakada T, Tsubouchi K, Kobayashi M, Kawai Y, Yano S, Matsunaga T, Hirose M, Ohmori S, Ohhashi T, Yamada M.


Decrease in the density of t-tubular L-type Ca2+ channel currents in failing ventricular myocytes.
Am J Physiol Heart Circ Physiol.,300:H978-H988 2011
Author:Horiuchi-Hirose M, Kashihara T, Nakada T, Kurebayashi N, Shimojo H, Shibazaki T, Sheng X, Yano S, Hirose M, Hongo M, Sakurai T, Moriizumi T, Ueda H, Yamada M.


Nicorandil ameliorates impulse conduction disturbances during ischemia in isolated arterially perfused canine atria.
Int J Cardiol.,146:37-43 2011
Author:Hirose M, Yano S, Nakada T, Horiuchi-Hirose M, Tsujino N, Yamada M.


Diacylglycerol kinase zeta inhibits ventricular tachyarrhythmias in a mouse model of heart failure.
Circ J. ,75:2333-2342 2011
Author:Hirose M, Takeishi Y, Niizeki T, Nakada T, Shimojo H, Kashihara T, Horiuchi-Hirose M, Kubota I, Mende U, Yamada M.


Mitochondrial ATP-sensitive K+ channels, protectors of the heart.
J Physiol. (Lond.),588:283-286 2010
Author:Yamada M.


Selective alpha1A-adrenoceptor stimulation induces Mueller's smooth muscle contraction in an isolated canine upper eyelid preparation.
Curr Eye Res,35:363-369 2010
Author:Yano S, Hirose M, Nakada T, Nakayama J, Matsuo K, Yamada M.


Effects of hormone-sensitive lipase disruption on cardiac energy metabolism in response to fasting and refeeding.
Am J Physiol Endocrinol Metab.,297:E1115-E1124 2009
Author:Suzuki J, Ueno M, Uno M, Hirose Y, Zenimaru Y, Takahashi S, Osuga J, Ishibashi S, Takahashi M, Hirose M, Yamada M, Kraemer FB, Miyamori I.


Diacylglycerol kinase zeta inhibits Galphsq-induced atrial remodeling in transgenic mice.
Heart Rhythm.,6:78-84 2009
Author:Hirose M, Takeishi Y, Niizeki T, Shimojo H, Nakada T, Kubota I, Nakayama J, Mende U, Yamada M.


Contribution of L-type Ca2+ channels to early afterdepolarizations induced by I Kr and I Ks channel suppression in guinea pig ventricular myocytes.
J Membr Biol.,222:151-166 2008
Author:Yamada M, Ohta K, Niwa A, Tsujino N, Nakada T, Hirose M.


MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of reactive oxygen species.
Cardiovasc Res.,78:554-562 2008
Author:Morimoto H, Hirose M, Takahashi M, Kawaguchi M, Ise H, Kolattukudy PE, Yamada M, Ikeda U.


Mechanisms of preventive effect of nicorandil on ischaemia-induced ventricular tachyarrhythmia in isolated arterially perfused canine left ventricular wedges.
Basic Clin Pharmacol Toxicol.,102:504-514 2008
Author:Hirose M, Tsujino N, Nakada T, Yano S, Imamura H, Yamada M.


Mutational analysis of block and facilitation of HERG current by a class III anti-arrhythmic agent, nifekalant.
Channels (Austin).,1:198-208 2007
Author:Hosaka Y, Iwata M, Kamiya N, Yamada M, Kinoshita K, Fukunishi Y, Tsujimae K, Hibino H, Aizawa Y, Inanobe A, Nakamura H, Kurachi Y.


Mechanisms of the preventive effect of pilsicainide on atrial fibrillation originating from the pulmonary vein.
Circ J.,71:1805-1814 2007
Author:Hirose M, Ohkubo Y, Takano M, Hamazaki M, Sekido T, Yamada M.


A functional role of the C-terminal 42 amino acids of SUR2A and SUR2B in the physiology and pharmacology of cardiovascular ATP-sensitive K+ channels.
J Mol Cell Cardiol.,39:1-6 2005
Author:Yamada M, Kurachi Y.


Phosphatidylinositol 3,4,5-trisphosphate and Ca2+/calmodulin competitively bind to the regulators of G-protein-signalling (RGS) domain of RGS4 and reciprocally regulate its action.
Biochem J.,385:65-73 2005
Author:Ishii M, Fujita S, Yamada M, Hosaka Y, Kurachi Y.


The nucleotide-binding domains of sulfonylurea receptor 2A and 2B play different functional roles in nicorandil-induced activation of ATP-sensitive K+ channels.
Mol Pharmacol.,65:1198-11207 2004
Author:Yamada M, Kurachi Y.


Mutation in nucleotide-binding domains of sulfonylurea receptor 2 evokes Na-ATP-dependent activation of ATP-sensitive K+ channels: implication for dimerization of nucleotide-binding domains to induce channel opening.
Mol Pharmacol.,66:807-816 2004
Author:Yamada M, Ishii M, Hibino H, Kurachi Y.


Comparison of kinetic properties of quinidine and dofetilide block of HERG channels.
Eur J Pharmacol.,493:29-40 2004
Author:Tsujimae K, Suzuki S, Yamada M, Kurachi Y.


Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes.
J Biol Chem.,279:44065-44073 2004
Author:Hibino H, Fujita A, Iwai K, Yamada M, Kurachi Y.


Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type KATP channels.
J Pharmacol Exp Ther.,304:1025-1032 2003
Author:Chachin M, Yamada M, Fujita A, Matsuoka T, Matsushita K, Kurachi Y.


Beta-adrenergic modulation of prepulse facilitation of L-type calcium channels in rabbit ventricular myocytes.
Pflugers Arch.,444:89-98 2002
Author:Yamada M.


The role of muscarinic K+ channels in the negative chronotropic effect of a muscarinic agonist.
J Pharmacol Exp Ther.,300:681-687 2002
Author:Yamada M.


The strongly inwardly rectifying background potassium channel (IK1) in cardiac myocytes is composed of Kir2.2 (IRK2): RT-PCR analysis of single cardiac myocyte mRNA.
Med J Osaka Univ.,44:15-22 2001
Author:Matsumoto Y, Isomoto S, Saito H, Inanobe A, Hibino H, Chachin M, Yamada M, Horio Y, Kurachi Y.


Tertiapin potently and selectively blocks muscarinic K+ channels in rabbit cardiac myocytes.
J Pharmacol Exp Ther.,293:196-205 2000
Author:Kitamura H, Yokoyama M, Akita H, Matsushita K, Kurachi Y, Yamada M.


Epinastine, a nonsedating histamine H1 receptor antagonist, has a negligible effect on HERG channel.
Eur J Pharmacol.,374:457-460 1999
Author:Chachin M, Katayama Y, Yamada M, Horio Y, Ohmura T, Kitagawa H, Uchida S, Kurachi Y.


G protein regulation of potassium ion channels.
Pharmacol Rev.,50:723-760 1998
Author:Yamada M, Inanobe A, Kurachi Y.


SUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil.
Br J Pharmacol.,124:985-991 1998
Author:Shindo T, Yamada M, Isomoto S, Horio Y, Kurachi Y.


Intracellular nucleotide-mediated gating of SUR/Kir6.0 complex potassium channels expressed in a mammalian cell line and its modification by pinacidil.
J Physiol. (Lond.),511:663-674 1998
Author:Satoh E, Yamada M, Kondo C, Repunte VP, Horio Y, Iijima T, Kurachi Y.


The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line, HEK293T cells.
Pflugers Arch.,435:595-603 1998
Author:Okuyama Y, Yamada M, Kondo C, Satoh E, Isomoto S, Shindo T, Horio Y, Kitakaze M, Hori M, Kurachi Y.


Identification and functional analysis of sulfonylurea receptor 1 variants in Japanese patients with NIDDM.
Diabetes.,47:476-481 1998
Author:Ohta Y, Tanizawa Y, Inoue H, Hosaka T, Ueda K, Matsutani A, Repunte VP, Yamada M, Kurachi Y, Bryan J, Aguilar-Bryan L, Permutt MA, Oka Y.


Chimeras of Kir6.1 and Kir6.2 reveal structural elements involved in spontaneous opening and unitary conductance of the ATP-sensitive K+ channels.
Recept Channels.,6:129-140 1998
Author:Kondo C, Repunte VP, Satoh E, Yamada M, Horio Y, Matsuzawa Y, Pott L, Kurachi Y.


Molecular aspects of ATP-sensitive K+ channels in the cardiovascular system.
Jpn J Physiol.,47 Suppl.:S4-S6 1997
Author:Isomoto S, Yamada M, Horio Y, Kurachi Y.


Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel.
J Physiol. (Lond.),499:715-720 1997
Author:Yamada M, Isomoto S, Matsumoto S, Kondo C, Shindo T, Horio Y, Kurachi Y.


Sur2 and Kcnj8 genes are tightly linked on the distal region of mouse chromosome 6.
Mamm Genome.,8:790-791 1997
Author:Isomoto S, Horio Y, Matsumoto S, Kondo C, Yamada M, Gilbert DJ, Copeland NG, Jenkins NA, Kurachi Y.


Expression and clustered distribution of an inwardly rectifying potassium channel, KAB-2/Kir4.1, on mammalian retinal Muller cell membrane: their regulation by insulin and laminin signals.
J Neurosci.,17:7725-7735 1997
Author:Ishii M, Horio Y, Tada Y, Hibino H, Inanobe A, Ito M, Yamada M, Gotow T, Uchiyama Y, Kurachi Y.


Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP90.
J Biol Chem.,272:12885-12888 1997
Author:Horio Y, Hibino H, Inanobe A, Yamada M, Ishii M, Tada Y, Satoh E, Hata Y, Takai Y, Kurachi Y.


An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4. 1), in cochlear stria vascularis of inner ear: its specific subcellular localization and correlation with the formation of endocochlear potential.
J Neurosci.,17:4711-4721 1997
Author:Hibino H, Horio Y, Inanobe A, Doi K, Ito M, Yamada M, Gotow T, Uchiyama Y, Kawamura M, Kubo T, Kurachi Y.


Specialized release zones in chromaffin cells examined with pulsed-laser imaging.
Cell Calcium.,20:181-201 1996
Author:Robinson IM, Yamada M, Carrion-Vazquez M, Lennon VA, Fernandez JM.


Competition between Mg2+ and spermine for a cloned IRK2 channel expressed in a human cell line.
J Physiol. (Lond.),493:143-156 1996
Author:Yamashita T, Horio Y, Yamada M, Takahashi N, Kondo C, Kurachi Y.


Cloning and functional expression of a novel isoform of ROMK inwardly rectifying ATP-dependent K+ channel, ROMK6 (Kir1.1f).
FEBS Lett.,399:122-126 1996
Author:Kondo C, Isomoto S, Matsumoto S, Yamada M, Horio Y, Yamashita S, Takemura-Kameda K, Matsuzawa Y, Kurachi Y.


A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel.
J Biol Chem.,271:24621-24324 1996
Author:Isomoto S, Kondo C, Yamada M, Matsumoto S, Higashiguchi O, Horio Y, Matsuzawa Y, Kurachi Y.


A novel ubiquitously distributed isoform of GIRK2 (GIRK2B) enhances GIRK1 expression of the G-protein-gated K+ current in Xenopus oocytes.
Biochem Biophys Res Commun.,218:286-291 1996
Author:Isomoto S, Kondo C, Takahashi N, Matsumoto S, Yamada M, Takumi T, Horio Y, Kurachi Y.


A functional model for G protein activation of the muscarinic K+ channel in guinea pig atrial myocytes. Spectral analysis of the effect of GTP on single-channel kinetics.
J Gen Physiol.,108:485-495 1996
Author:Hosoya Y, Yamada M, Ito H, Kurachi Y.


Spermine gates inward-rectifying muscarinic but not ATP-sensitive K+ channels in rabbit atrial myocytes. Intracellular substance-mediated mechanism of inward rectification.
J Biol Chem.,270:9289-9294 1995
Author:Yamada M, Kurachi Y.


A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells.
J Biol Chem.,270:16339-16346 1995
Author:Takumi T, Ishii T, Horio Y, Morishige K, Takahashi N, Yamada M, Yamashita T, Kiyama H, Sohmiya K, Nakanishi S, et al.


Molecular and functional heterogeneity of inward rectifier potassium channels in brain and heart.
Heart Vessels.,Supple. 9:8-11 1995
Author:Takahashi N, Morishige K-I, Yamada M, Takumi T, Kurachi Y.


Gbg directly binds to the carboxyl terminus of the G protein-gated muscarinic K+ channel, GIRK1
Biochem Biophys Res Commun.,212:1022-1028 1995
Author:Inanobe A, Morishige KI, Takahashi N, Ito H, Yamada M, Takumi T, Nishina H, Takahashi K, Kanaho Y, Katada T, et al.


Regulation of potassium channels by G-protein subunits and arachidonic acid metabolites.
Methods Enzymol.,238:394-422 1994
Author:Yamada M, Terzic A, Kurachi Y.


Muscarinic K+ channels are activated by beta gamma subunits and inhibited by the GDP-bound form of alpha subunit of transducin.
Biochem Biophys Res Commun.,200:1484-1490 1994
Author:Yamada M, Ho YK, Lee RH, Kontanill K, Takahashill K, Katadall T, Kurachi Y.


Molecular cloning and functional expression of cDNA encoding a second class of inward rectifier potassium channels in the mouse brain.
J Biol Chem.,269:23274-23279 1994
Author:Takahashi N, Morishige K, Jahangir A, Yamada M, Findlay I, Koyama H, Kurachi Y.


Molecular cloning and functional expression of a novel brain-specific inward rectifier potassium channel.
FEBS Lett.,346:251-256 1994
Author:Morishige K, Takahashi N, Jahangir A, Yamada M, Koyama H, Zanelli JS, Kurachi Y.


Cardiovascular profile of E4080 and its analogue ER001533: Novel potassium channel openers with bradycardiac properties.
Drug Rev.,11:223-233 1993
Author:Terzic A, Tung RT, Shen WK, Yamada M, Kurachi Y.


YM934, a novel K+ channel opener, activates ATP-sensitive K+ channels in cardiac myocytes.
J Pharmacol Exp Ther.,267:1544-1549 1993
Author:Yamada M, Terzic A, Findlay I, Jahangir A, Shen WK, Kurachi Y.


GK* and brain Gbg activate muscarinic K+ channel through the same mechanism.
J Biol Chem.,268:24551-24554 1993
Author:Yamada M, Jahangir A, Hosoya Y, Inanobe A, Katada T, Kurachi Y.


Lysophosphatidylcholine inhibits bradykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells.
Circ Res.,71:1410-1421 1992
Author:Inoue N, Hirata K, Yamada M, Hamamori Y, Matsuda Y, Akita H, Yokoyama M.


P2-purinoceptor activation stimulates phosphoinositide hydrolysis and inhibits accumulation of cAMP in cultured ventricular myocytes.
Circ Res.,70:477-485 1992
Author:Yamada M, Hamamori Y, Akita H, Yokoyama M.


5-Hydroxytryptamine induces phospholipase C-mediated hydrolysis of phosphoinositides through 5-hydroxytryptamine-2 receptors in cultured fetal mouse ventricular myocytes.
Circ Res.,66:1474-1483 1990
Author:Hamamori Y, Yokoyama M, Yamada M, Akita Makin, Goshima K, Fukuzaki H.


講演・口頭発表等
神経障害性疼痛へのHCN チャネルの関与
第100回日本生理学会大会 2023(Mar. 15)
Presenter:山田充彦、張昊、柏原俊英、中田勉、田中聡、石田公美子、布施谷仁志、川岸裕幸、中村博之、清沢研一、川真田樹人


心不全治療薬としてのレニン・アンジオテンシン・アルドステロン系抑制薬:その薬理と臨床(基礎編)
第96回日本薬理学会年会 2022(Dec. 03)
Presenter:山田充彦


Molecular Mechanism underlying Initiation & Maturation of Heartbeat
第99回日本生理学会大会 2022(Mar. 17)
Presenter:Mitsuhiko Yamada, Tomoe Nakamura-Nishitani


低分子βアレスチンバイアスAT1受容体アゴニストの開発
第95回日本薬理学会年会 2022(Mar. 07)
Presenter:山田充彦、小松弘嗣


T1アンジオテンシン受容体を利用した新たな胎児・新生児心不全治療法の開発
日本胎児心臓病学会第28回学術集会 2022(Feb. 18)
Presenter:山田充彦


Cardiac AT1 receptor/-arrestin axis is a novel druggable target for pediatric heart failure
The 12th Annual Meeting of Japanese Safety Pharmacology Society 2021(Mar. 12)
Presenter:Mitsuhiko Yamada, Hiroyuki Kawagishi, Shin Kadota, Cheng-Kun Du, Yuji Shiba, Sachio Morimoto


Cardiac AT1 receptor/-arrestin pathway is a neonatal-specific druggable target for pediatric heart failure.
CVMV2021 2021(Mar. 12)
Presenter:Mitsuhiko Yamada


小児疾患治療薬の新たな薬物標的の探索
第94回日本薬理学会年会 2021(Mar. 09)
Presenter:山田充彦


Postnatal loss of gp130 caused impaired cardiac contractility accompanied by inhibition of physiological proliferation of cardiomyocytes.
NIPS International Meeting on Cardiovascular Physiology 2020 2020(Dec. 25)
Presenter:Hiroyuki Kawagishi, Tsutomu Nakada, Takuro Numaga-Tomita, Mitsuhiko Yamada


小児心不全では、AT1アンジオテンシン受容体を抑制すべきか刺激すべきか?
第56回日本小児循環器学会総会・学術集会 2020(Nov. 24)
Presenter:山田充彦


Molecular mechanism underlying cardiac early afterdepolarization induced by IKr and IKs suppression.
The 11th Annual Meeting of Japanese Safety Pharmacology Society 2020(Feb. 28)
Presenter:Yamada, M.


新生児マウスにおける、gp130受容体を介した心筋細胞の発達機構
筋生理の集い 2019(Dec. 21)
Presenter:川岸裕幸、Maite LARRA AGA、冨田(沼賀)拓郎、中田勉、山田充彦


A beta arrestin-bias AT1 receptor agonist improves the survival of neonatal knock-in mice bearing a human dilated cardiomyopathy mutation.
The 50th NIPS International Symposium. ‘MIRACLES’ in Cardiovascular Physiology 2019(Dec. 04)
Presenter:Yamada, M.


βアレスチンバイアスアンジオテンシン1型受容体アゴニストは、新生児マウス心臓において持続的な陽性変力作用を示す
第29回日本循環薬理学会 2019(Nov. 29)
Presenter:川岸裕幸、柏原俊英、中田勉、冨田拓郎、山田充彦


心室筋活動電位内でのL型Ca2+電流波形を決定する分子機構の検討
学術セミナー「分子から個体へ:俯瞰と接近の生命科学」 2019(Oct. 18)
Presenter:山田充彦、西村仁志、柏原俊英


Molecular mechanisms underlying the agonistic effect of FPL64176 on CaV1.2 Ca2+ channels
第141回日本薬理学会関東部会 2019(Oct. 12)
Presenter:冨田拓郎、五味志文、柏原俊英、中田勉、山田充彦


小胞体CaセンサーSTIM1によるCav1.2チャネル制御機構の解明
第66回中部日本生理学会 2019(Oct. 04)
Presenter:冨田拓郎、高橋弘毅、山田充彦


除神経モデルマウスの骨格筋におけるホスホランバンの発現量の増加
第66回中部日本生理学会 2019(Oct. 04)
Presenter:中田勉、小松雅俊、山田充彦


マウス心筋細胞の生下後の機能的最終分化のメカニズムの解析
第140回日本薬理学会関東部会 2019(Jul. 06)
Presenter:川岸裕幸、中田勉、山田充彦


EP4 receptor-mediated augmentation of Ih currents in A DRG neurons underlies neuropathic pain.
FAOPS 2019 2019(Mar. 29)
Presenter:Yamada, M., Zhang, H., Kashihara, T., Nakada, T., Tanaka, S., Ishida, K., Fuseya, S., Kawagishi, H., Kiyosawa, K., Kawamata, M.


Interaction of junctophilins and the CaV1.1 is essential for the skeletal muscle contraction.
FAOPS 2019 2019(Mar. 29)
Presenter:Nakada, T., Kashihara, T., Komatsu, M., Yamada, M.


マウス個体を用いた心筋細胞成熟化因子の同定
第92回日本薬理学会年会 2019(Mar. 16)
Presenter:川岸裕幸、中田勉、山田充彦


c-Srcによる全長型CaV1.2サブユニットを有するL型Ca2+チャネルの活性を介したPDGFによる増殖型血管平滑筋細胞の遊走
第92回日本薬理学会年会 2019(Mar. 15)
Presenter:中田勉、郭暁光、柏原俊英、青山俊文、山田充彦


プロスタノイドEP4受容体を介する後根神経節A細胞のIh電流増強による神経障害性疼痛の発症
第92回日本薬理学会年会 2019(Mar. 15)
Presenter:山田充彦、張昊、柏原俊英、中田勉、田中聡、石田公美子、布施谷仁志、川岸裕幸、清沢研吉、川眞田樹人


Molecular mechanisms underlying spatiotemporal regulation of L-type Ca2+ channels in muscles. Logic of life: ion channel structure, function and physiology.
International commemorative symposium in celebration of retirement of Professor Yoshihisa Kurachi 2019(Mar. 13)
Presenter:Yamada, M.


G蛋白サブユニットGαoのCa2+handling恒常性および心収縮能維持における意義の解明
日本臨床分子医学会学術総会プログラム・抄録集 55回 51 2018(Apr.)
Presenter:稲住 英明, 桑原 宏一郎, 桑原 佳宏, 中川 靖章, 木下 秀之, 錦見 俊雄, 呉林 なごみ, 山田 充彦, 柏原 俊英, 中尾 一和, 木村 剛


HFpEFにおける心筋興奮収縮連関の変化
日本循環器学会学術集会抄録集 81回 TP7-4 2017(Mar.)
Presenter:山田 充彦, Kashihara Toshihide


Cardiac AT Receptor/β-Arrestin Pathway is a Neonatal-Specific Druggable Target for Pediatric Heart Failure
Experimental Biology 2021 0427( 21)
Presenter:Mitsuhiko Yamada, Hiroyuki Kawagishi, Shin Kadota, Yuji Shiba, Sachio Morimoto


MISC
βアレスチンバイアスAT1受容体アゴニストは新しい乳幼児心不全治療薬の有力候補である。
医学のあゆみ,276(12):1137-1138 2021(Mar. 20)

共同研究等希望テーマ
イオンチャネル作動薬の開発と解析 , 薬理学一般
小児心不全治療薬 , 小児循環器内科 , 小児心不全治療薬の開発
研究費
共同研究
2021 - , Application of a beta-arrestin-biased agonist, TRV027 to pediatric heart failure , 国際共同研究
2020 - , 小分子βアレスチンバイアスAT1受容体アゴニストの開発 , その他

受託研究
2021 - 2022 , 離乳期までの心筋細胞AT1受容体のダイナミックな生命維持機能を活用した世界初低分子小児心不全治療薬の開発
2008 - 2009 , Gqマウス心不全モデルを用いたニコランジルの心筋繊維化への抑制効果
2008 - 2009 , 新規Caチャネル阻害薬を用いた、がん細胞の増殖抑制法の研究
2007 - 2009 , イオンチャネルとトランスポーターのクロストークに関するkrん旧
2007 - 2008 , 虚血による貫壁性活動電位幅不均一性に対するNicorandilの抑制効果
2007 - 2008 , 新規Caチャネル阻害薬を用いた、がん細胞の増殖抑制法の研究
2006 - 2007 , イヌ虚血心室筋の頻拍性不整脈発生に対するニコランジルの保護効果
2006 - 2007 , 新規Caチャネル阻害薬を用いた、がん細胞の増殖抑制法の研究
2005 - 2006 , 虚血による貫壁性活動電位幅不均一性に対するNicorandilの抑制効果

科学研究費補助金(研究代表者)
2023 - 2026 , 心筋細胞AT1受容体に共役する信号伝達経路の発達依存的変化の意義と機序の解明 , 基盤研究(C)(一般)
2018 - 20200331 , 生下後の心筋分化誘導因子の同定:インビトロ心筋最終分化誘導法の開発 , 基盤研究(C)
2009 - 2011 , L型カルシウムチャネル阻害薬の開口状態親和性の定量的解析と阻害薬作用のモデル化 , 基盤研究(C)
2004 - 2006 , 薬物によるATP感受性K+チャネルの活性調節機構の立体構造基盤の解明 , 基盤研究(C)
2004 - 2006 , 薬物によるATP感受性K+チャネルの活性調節機構の立体構造基盤の解明 , 基盤研究(C)
2000 - 2002 , 副交感性心拍調節におけるムスカリン性Kチャネルの役割の検討 , 基盤研究(C)
1996 - 1997 , 内向き整流カリウムチャネルのポリアミン受容体の解析と新しい潜在的薬物作用点の検討 , 一般研究B
1995 - 1995 , 内向き整流カリウムチャネルの細胞内物質によるゲーテイング , 奨励研究A

科学研究費補助金(研究分担者)
1997 - 1998 , 動脈硬化血管の収縮異常と血管平滑筋型ATP感受性K+チャネル , 特定領域研究A

奨学寄附金
2018 , AT1アンジオテンシン受容体βアレスチンバイアスアゴニストが若年性心不全に与える効果の検討
2018 , サルコペニアにおいて筋⼒低下が⽣じるメカニズムの解明
2018 , βアレスチンバイアスAT1受容体アゴニストを⽤いた⼩児⼼不全治療法の開発
2018 , ⼩児⼼不全の新しい薬物療法の開発
2018 , ⼩児⼼不全の新しい治療法の開発
2018 , βアレスチンバイアスAT1受容体アゴニストを⽤いた⼩児⼼不全治療法の開発
2018 , ⼩児⼼不全の新しい治療法の開発
2017 , βアレスチンバイアスAT1受容体アゴニストを⽤いた⼩児⼼不全治療法の開発
2017 , ⼩児⼼不全の新しい薬物療法の開発
2017 , AT1アンジオテンシン受容体βアレスチンバイアスアゴニストが若年性心不全に与える効果の検討
2017 , βアレスチンバイアスAT1受容体アゴニストを⽤いた⼩児⼼不全治療法の開発
2017 , βアレスチンバイアスAT1受容体アゴニストを⽤いた⼩児⼼不全治療法の開発
2016 , AT1アンジオテンシン受容体βアレスチンバイアスアゴニストが若年性心不全に与える効果の検討
2016 , 心不全の心室筋細胞でのL型Ca2+チャネルのリモデリングに関する研究
これまでにない⽅法でAT1アンジオテンシン受容体(AT1R)を利⽤した⼩児⼼ 不全治療法の開発
⼼筋ジャンクトフィリン2の発現・機能異常が,⼼不全・不整脈などの病態形成に与える影響の検討
選択的βアレスチン刺激による小児心不全治療法の開発

その他公的資金
2000 - 2002 , 心筋細胞の再生療法に関する研究:心筋細胞の電気生理学的分化とその制御因子の同定
1999 - 2001 , カルシウムチャネルによる心・血管細胞収縮調節機構とその異常
研究諸活動
その他研究活動
2021- , 「子どもの薬を創る会」講演会定期開催主催 , 専門家に小児創薬の諸問題をオンライン講演頂く。

教育活動実績

授業等
2022 , 薬理学総論
2018 , 前期 , 器官・組織・細胞機能研究方法特論
2004 , 薬理学演習・実習

社会活動実績

社会活動等
公開講座
20201025 - 20201025 , 市民公開講座:心不全の予防・診療・リハビリテーションの最前線

学会・研究会の主催等
20221013 - 20221014 , 生理研研究会「心血管研究会」 , 提案代表者
20211118 - 20211119 , 生理研研究会「心血管研究会」 , 提案代表者
20201024 - 20201024 , 第143回日本薬理学会関東部会 , 部会長
20161202 - 20161202 , 第26回日本循環薬理学会 , 当番幹事

メディア・報道
20201207 , 日本経済新聞 , ペプチドで小児心不全治療 小児用創薬のヒントに
20201130 , 信濃毎日新聞 , 新生児や乳児の心臓 収縮力を高める仕組み解明