2007 Fiscal Year Final Research Report Summary
Analyses of calcium-activated potassium channels as novel targets for new drug therapy
| Project/Area Number |
17390045
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
IMAIZUMI Yuji Nagoya City University, Graduate School of Pharmaceutical Sciences, Professor (60117794)
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| Co-Investigator(Kenkyū-buntansha) |
OHYA Susumu Nagoya City University, Graduate School of Pharmaceutical Sciences, Associate Professor (70275147)
YAMAMURA Hisao Nagoya City University, Graduate School of Pharmaceutical Sciences, Research Associate (80398362)
TOGARI Akihumi Aichi Gakuin University, School of Dentistry, Professor (80126325)
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| Project Period (FY) |
2005 – 2007
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| Keywords | calcium-activated potassium channel / BK channel / SK channel / potassium channel opener / ryanodine receptor / caveolae / drug development / potential sensitive fluorescent |
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| Research Abstract |
In excitable cells, such as CNS neurons, negative feedback regulation systems for intracellular Ca^<2+> homeostasis work to prevent Ca^<2+> overlord, when excess excitability and resulting excess Ca^<2+> influx occurs. Activation of Ca^<2+> activated K+ (Kca) channels is know to be one ` of the most important components responsible for the negative feedback regulation of [Ca2^+]_i in excitable cells. This project was undertaken to elucidate the molecular mechanism for the regulation of Kca channel activity and to search changes in the regulation diseases. The goal of this project is to find out molecular seeds targeting on K_ca channels in some diseases. The following development was obtained during the research period. (1) It was found that small conductance K_ca (SK) channel in vascular endothelial cell lines originally derived from bovine blood-brain barrier has significant functional role in endothelial; proliferation stimulated by ATP presumably released from astrocytes in CNS. (J
… More
BC,2006; J Pharmacol Sci, 104, 2007). (2) The deep impact of ryanodine receptor type2 (RyR2) to the mechanism for negative feedback regulation of [Ca^<2+>], via spontaneous Ca^<2+> release(Ca^<2+> spark) from sarcoplasmic reticulum and subsequent activation of large conductance Kca (BK) channel was found using urinary bladder smooth muscle cells from wild type and RyR2 heterozygous KO mice. A line of evidence indicates that RyR2 contributes to the bladder continent as 'a key molecule regulating resting membrane potential and muscular tonus as well as excitation-contraction coupling (J Physiol, 2007, J Pharmacol Sci, 103, 2007). (3) It was found that potential sensitive oxonol dyes act as potent BK channel openers. It is the first synthesized compound which shows opening property selective to BK81 and 84 subunits over BK62. The oxonol compounds may be a seed of 8 subunit selective BK channel opener (Mol Pharmacol, 2007). (4) It has been known that the contractile responses of isolated large arteries from spontaneously hypertensive rats (SHR) to agonists are markedly potentiated in low pH bathing solution. It was found that the enhanced expression of BK channels in arterial smooth muscles of SHR and its sensitivity to extracellular pH are responsible for the acid pH induced potentiation of contraction (Am J Physiol, 2007). Less
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Research Products
(215 results)
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[Journal Article] Ryanodine receptor type 2 deficiency changes excitation- contraction coupling and membrane potential in urinary bladder smooth muscle2007
Author(s)
Shingo, Hotta, Kozo, Morimura, Susumu, Ohya, Katsuhiko, Muraki, Hiroshi, Takesmma, Yuji, Imaizum
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Journal Title
J. Physiol. (Lond.) 582
Pages: 489-506
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Voltage-Sensitive Oxonol Dyes Are Novel Large-Conductance Ca^<2+> -Activated K^+ channel Activators Selective for 131 and 34 but Not for β 2 Subunits2007
Author(s)
Takashi, Morimoto, Kazuho, Sakamoto, Hiroko, Sade, Susumu, Ohya, KatsunlKo, Muraki, Yuji, Imaizumi
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Journal Title
Mol.Pharmacol 71
Pages: 1075-1088
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A new insight into the function of TRPV22006
Author(s)
Muraki K
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Journal Title
circulatory organs TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades(Frontiers in Neuroscience)(Wolfgang B. Liedtke, ed.), Chapter 28, CRC Press
Pages: 389-396
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Novel functions of small conductance Ca^<2+>-activated K+ channel in enhanced cell proliferation by ATP in Brain Endothelial Cells J. Biol. Chem2006
Author(s)
Daiju, Yamazaki, Mineyoshi, Aoyama, Susumu, Ohya, Katsuhiko, Muraki, Kiyofumi, Asai, Yuji, Imaizumi
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Journal Title
J. Biol. Chem 281
Pages: 38430-38439
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular and electrophysiological characteristics of K^+ conductance sensitive to acidic pH in aortic smooth muscle cells of WKY and SHR2006
Author(s)
Hidekazu, Kiyoshi, Daiju, Yamazaki, Susumu, Ohya, Mika, Kitsukawa, Katsuhiko, Muraki, Shinya, Saito, Yasushi, Ohizumi, Yuji, Imaizumi
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Journal Title
Am. J. Physiol. Heart Circ. Physiol 291
Pages: H2723-H2734
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inherent pacemaker function of duodenal GIST2006
Author(s)
Shinji, Furuzono, Susumu, Ohya, Soichiro, Inoue, Akimasa, Nakao, Yuji, Imaizumi, Shinsuke, Nakayama
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Journal Title
Eur. J. Cancer 42
Pages: 243-248
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular, Mechanisms, for Large, Conductance Ca^<2+>-Activated K+ Channel Activation by a Novel Opener, 12,14-Dichlorodehydroabietic Acid2006
Author(s)
Kazuho, Sakamoto, Taro, Nonomura, Susumu, Ohya, Katsuhiko, Muraki, Tomohiko, Ohwada, Yuji, Imaizumi
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Journal Title
J. Pharmacol. Exp. Ther 316
Pages: 144-153
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Two-step Ca^<2+> intracellular release underlies excitation-contraction coupling in mouse urinary bladder myocytes2006
Author(s)
Kozo, Morimura, Yoshiaki, Ohi, Hisao, Yamamura, Susumu, Ohya, Katsuhiko, Muraki, Yuji, Imaizumi
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Journal Title
Am. J. Physiol. Cell Physiol 290
Pages: C388-C403
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Activation of large-conductance, Ca^<2+>-activated K^+ channels by cannabinoids Am2006
Author(s)
Hiroko, Sade, Katsuhiko, Muraki, Susumu, Ohya, Noriyuki, Hatano, Yuji, Imaizumi
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Journal Title
J. Physiol. Cell Physiol 290
Pages: C77-C86
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Sulphonylurea receptors differently modulate ICC pacemaker Ca^<2+> activity and smooth muscle contractility2005
Author(s)
Shinsuke, Nakayama, Susumu, Ohya, Hong-Nian, Liu, Toshiya, Watanabe, Shinji, Furuzono, Jing, Wang, Yuji, Nishizawa, Masahiro, Aoyama, Naruhiko, Murase, Tatsuaki, Matsubara, Yasushi, Ito, Yuji, Imaizumi, Shunichi, Kajioka
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Journal Title
J. Cell Sci 118
Pages: 4163-4173
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] K^+ Currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts2005
Author(s)
Lisa, Chilton, Susumu, Ohya, Darren, H., Freed, Eric, George, Vanja, Drobic, Yoshiyuki, Shibukawa, K., Andrew Mac, Cannell, Yuji, Imaizumi, Robert, B. Clark, Ian, M. C., Dixon, Wayne, R. Giles
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Journal Title
Am. J. Physiol. Heart Circ. Physiol 288
Pages: H2931-H2939
Description
「研究成果報告書概要(欧文)」より
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[Presentation] TIRF imaging of BK channel molecules2008
Author(s)
Chikako, Ikeda, Hisao, Yamamura, Susumu, Ohya, Yuji, Imaizumi
Organizer
The 81st Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Yokohama
Year and Date
2008-03-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Gene expression of Ca^<2+>-activated K^+ channels in human prostate cancer2007
Author(s)
Satomi, Niwa, Susumu, Ohya, Akitoshi, Ohno, Yoshiyuki, Kojima, Syoichi, Sasaki, Kenjiro, Kori, Yuji, Imaizumi
Organizer
The 17th Annual Metting of Japanese Society of Pharmaceutical Health Care and Sciences
Place of Presentation
Gunma
Year and Date
2007-09-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of ONO-WE-061, a novel agonist for S1P receptor, in rabbit sinus node cells2007
Author(s)
Makoto, Iwaanmi, Katsuhiko, Muraki, Hisao, Yamamura, Susumu, Ohya, Yuji, Imaizumi
Organizer
The 127th Annual Meeting of The Pharmaceutical Society of Japan
Place of Presentation
Toyama
Year and Date
2007-03-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Gene profiles of ion channels in human prostate cancer2007
Author(s)
Satomi, Niwa, Susumu, Ohya, Akitoshi, Ohno, Yoshiyuki, Kojima, Syoichi, Sasaki, Kenjiro, Kori, Yuji, Imaizumi
Organizer
The 127th Annual Meeting of The Pharmaceutical Society of Japan
Place of Presentation
Toyama
Year and Date
2007-03-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The excess membrane hyperpolarization induced by Kir2.1 activation causes brain capillary endothelial cell death2007
Author(s)
Daiju, Yamazaki, Hisao, Yamamura, Susumu, Ohya, Ktsuhiko, Muraki, Kiyofumi, Asai, Yuji, Imaizumi
Organizer
The 80th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Nagoya
Year and Date
2007-03-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Changes in Ca^<2+> mobilization in urinary bladder smooth muscle overexpressing Na+/ Ca^<2+> exchanger (NCX)2007
Author(s)
Shingo, Hotta, Hidemichi, Murata, Hisao, Yamamura, Susumu, Ohya, Takahiro, Iwamoto, Yuji, Imaizumi
Organizer
The 80th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Nagoya
Year and Date
2007-03-14
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Expression of K^+ and Ca^<2+> channel genes in human prostate cancer2007
Author(s)
Susumu, Ohya, Satomi, Niwa, Akitoshi, Ohno, Kojima, Shoichi, Sasaki, Kenjiro, Kohri, Yuji, Imaizumi
Organizer
The 80th Annual Meeting of the Pharmacological Society of Japan
Place of Presentation
Nagoya, Japan
Year and Date
2007-03-14
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Pharmacological analysis of novel large-conductance Ca^<2+> activated K^+ channel openers2006
Author(s)
Takeshi, Morimoto, Kazuho, Sakamoto, Hiroko, Sade, Susumu, Ohya, Katsuhiko, Muraki, Yuji, Imaizumi
Organizer
The 110th Kinki Branch Meeting of the Pharmacological Society of Japan in Kyoto
Place of Presentation
Kyoto
Year and Date
2006-11-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Testosterone regulation of ion channel expression in vas deferens2006
Author(s)
Susumu, Ohya, Akitoshi, Ohno, Satomi, Niwa, Katsutoshi, Ito, Katsuhiko, Muraki, Yuji, Imaizumi
Organizer
The 34th Symposium on Drug Activity
Place of Presentation
Takasaki, Japan
Year and Date
2006-09-29
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Changes in physiological function in urinary bladder smooth muscles overexpressing Na^+/Ca^<2+> exchanger (NCX)2006
Author(s)
Shingo, Hotta, Hidemichi, Murata, Hisao, Yamamura, Susumu, Ohya, Takahiro, Iwamoto, Yuji, Iwamoto
Organizer
The 48th Annual Meeting of Japan Society of Smooth Muscle Research
Place of Presentation
Okayama
Year and Date
2006-07-20
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The contribution of ryanodine receptor type 2 to E℃ coupling and the regulation of resting tone in urinary bladder myocytes2006
Author(s)
Shingo, Hotta, Kozo, Morimura, Susumu, Ohya, Katsuhiko, Muraki, Hiroshi, Takeshima, Yuji, Imaizumi
Organizer
IUPHAR -15th World Congress of Pharmacology-
Place of Presentation
Beijing, China
Year and Date
2006-07-06
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Two different types of K^+ channels regulated cell proliferation and cell death in bovine brain endothelial cells2006
Author(s)
Daiju, Yamazaki, Susumu, Ohya, Katsuhiko, Muraki, Kiyofumi, Asai, Yuji, Imaizumi
Organizer
IUPHAR -15th World Congress of Pharmacology-
Place of Presentation
Beijing, China
Year and Date
2006-07-04
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Down-regulation of intermediate conductance Ca^<2+> activated K^+ channel in smooth muscle of voltage dependent Ca2+ channel(32)subunit deficient mouse2006
Author(s)
Kozo, Morimura, Susumu, Ohya, Hisao, Yamamura, Manabu, Murakami, katsuhiko, muraki, Kazuo, Nunoki, Teruyuki, Yanagisawa, Yuji, Imaizumi
Organizer
The 79th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Yokohama
Year and Date
2006-03-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Cell-cycle dependent regulation of small-conductance Ca^<2+> -activated K^+ channel activity in Jurkat T-lymphocytes2006
Author(s)
Takeshi, Morimoto, Susumu, Ohya, Hidetoshi, Hayashi, Katsuhiko, Muraki, Kikuo, Onozaki, Yuji, Imaizumi
Organizer
The 79th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Yokohama
Year and Date
2006-03-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of 4a-Phorbol 12,13-dide-canoate, a potent activator of Trpv4, on intracellular Ca^<2+> concentration and membrane currents in rat aortic myocytes2006
Author(s)
Ryoichi, Tanaka, Katsuhiko, Muraki, Susumu, Ohya, Yuji, Imaizumi
Organizer
The 79th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Yokohama
Year and Date
2006-03-09
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Ca^<2+> mobilization via ryanodine receptor type 2 in urinary bladder smooth muscle2006
Author(s)
Shingo, Hotta, Kozo, Morimura, Susumu, Ohya, Katsuhiko, Muraki, Hiroshi, Takeshima, Yuji, Imaizumi
Organizer
The 79th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Yokohama
Year and Date
2006-03-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Changes in intermediate-conductance Ca^<2+> -activated K^+ channel expression in smooth muscles of voltage-gated Ca^<2+> channel β3 subunit null mice2005
Author(s)
Kozo, Morimura, Susumu, Ohya, Hisao, Yamamura, Manabu, Murakami, Katsuhiko, Muraki, Kazuo, Nunoki, Teruyuki, Yanagisawa, Yuji, Imaizumi
Organizer
Tokai Brunch Meeting of The Japanese Pharmaceutical Society 2005
Place of Presentation
Nagoya
Year and Date
2005-12-03
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Two types of K^+ channel regulate cell proliferation and damage in bovine brain capillary endothelial cells2005
Author(s)
Daiju, Yamazaki, Mineyoshi, Aoyama, Susumu, Ohya, Katsuhiko, Muraki, Kiyofumi, Asai, Yuji, Imaizumi
Organizer
Neuroscience 2005 -SfN 35th Annual Meeting-
Place of Presentation
Washington DC, USA
Year and Date
2005-11-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Changes in functional expression of voltage-dependent Ca^<2+> channel and the ryanodine receptor during cardiac myocytes differentiation in P19CL6 cells2005
Author(s)
Yuko, Hori, Kaori, Kato, Asuka, Ogawa, Kozo, Morimura, Shingo, Hotta, Hisao, Yamamura, Susumu, Ohya, Katsuhiko, Muraki, Yuji, Imaizumi
Organizer
Biofunction and Drug Discovery Symposium 2005
Place of Presentation
Hiroshima
Year and Date
2005-09-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Imaizumi A model for electrical pacemaker cells of the gut〜Functional coupling between ryanodine receptor and Ca^<2+>-activated K^+ channel〜2005
Author(s)
Taisuke, Kimura, Hisao, Yamamura, Aid, Yamada, Takayo, Goto, Susumu, Ohya, Katsuhiko, Muraki, Yuji, Imaizumi
Organizer
Biofunction and Drug Discovery Symposium 2005
Place of Presentation
Hiroshima
Year and Date
2005-09-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Expression of BK channel β1 subunit in cardiac mitochondria and cardioprotective effects of BK channel openers2005
Author(s)
Susumu, Ohya, Kazuho, Sakamoto, Yukiko, Kuwata, Katsuhiko, Muraki, Tomohiko, Ohwada
Organizer
Biofunction and Drug Discovery Symposium 2005
Place of Presentation
Hiroshima, Japan
Year and Date
2005-09-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Physiological functions of ryanodine receptor type 2 (RyR2) at resting state and during excitation-contraction coupling in urinary bladder smooth muscle2005
Author(s)
Shingo, Hotta, Kozo, Morimura, Susumu, Ohya, Katsuhiko, Muraki, Hiroshi, Takeshima, Yuji, Imaizumi
Organizer
University of Oxford Meeting on Ion channels, genes and regulation in smooth muscle.
Place of Presentation
Oxford. UK
Year and Date
2005-09-05
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Significance of RyR2 in EC coupling in urinary bladder2005
Author(s)
Shingo, Hotta, Kozo, Morimura, Susumu, Ohya, Katsuhiko, Muraki, Hiroshi, Takeshima, Yuji, Imaizumi
Organizer
The 47th Annual Meeting of Japan Society of Smooth Muscle Research
Place of Presentation
Sendai
Year and Date
2005-07-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Intracellular Ca^<2+> mobilization in urinary bladder of RyR2 heterozygous KO mice2005
Author(s)
Shingo, Hotta, Kozo, Morimura, Susumu, Ohya, Katsuhiko, Muraki, Hiroshi, Takeshima, Yuji, Imaizumi
Organizer
The 82nd Annual Meeting of The Physiological Society of Japan
Place of Presentation
Sendai
Year and Date
2005-05-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Novel mechanism for enhancement of Ca^<2+> response to ATP in bovine brain capillary endothelial cells2005
Author(s)
Yuji, Imaizumi, Daiju, Yamazaki, Mineyoshi, Aoyama, Susumu, Ohya, Katsuhiko, Muraki, Kiyofumi, Asai
Organizer
The 35th Congress of the International Union of Physiological Sciences (IUPS)
Place of Presentation
San Diego, USA
Year and Date
2005-04-03
Description
「研究成果報告書概要(欧文)」より
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