Junctional membrane-targeting mechanism of cardiac L-type calcium channel

• Project/Area Number: 22790206
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General physiology
• Research Institution: Shinshu University
• Principal Investigator: NAKADA Tsutomu 信州大学, 医学部, 助教 (70452141)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: L型カルシウムチャネル / リアノジン受容体 / 心筋 / 生理学 / 循環器・高血圧 / カプロン

Research Abstract

In cardiac myocytes, L-type calcium channels(LTCC) form a functional signaling complex with ryanodine receptors at the junctional membrane(JM). Although the specific localization of LTCCs to JM is critical for excitation-contraction coupling, their targeting mechanism is unclear. To identify the sequences of a_<1C> responsible for the JM-targeting, we generated various mutants of aic subunit, and studied their targeting properties in dysgenic(a_<1S.-null) GLT myotubes. The results revealed that amino acids^<1681> LQAGLRTL^<1688> and^<1693> PEIRRAIS^<1700> predicted to form two adjacent a-helices in the proximal C-terminus are necessary for the JM-targeting of a_<1C>.

Research Products

• [Journal Article] Chronic receptor-mediated activation of Gi/o proteins alters basal t-tubular and sarcolemmal L-type Ca^<2+> channel activity through phosphatases in heart failure (2012)
  • Author(s): Kashihara, T., Nakada, T., Shimojo, H., Horiuchi-Hirose, M., Gomi, S., Shibazaki, T., Sheng, X., Hirose, M., Hongo, M., and Yamada, M
  • Journal Title: Am. J. Physiol. Heart Circ. Physiol Volume: 302 Issue: 8 Pages: 1645-1654
  • DOI: 10.1152/ajpheart.00589.2011
  • Peer Reviewed
• [Journal Article] Diacylglycerol KinaseζInhibits Ventricular Tachyarrhythmias in a Mouse Model of Heart Failure (2011)
  • Author(s): Hirose M, Takeishi Y, Niizeki T, Nakada T, Shimojo H, Kashihara T, Horiuchi-Hirose M, Kubota I, Mende U, Yamada M.
  • Journal Title: Circ. J Volume: 75 Pages: 2333-2342
  • Peer Reviewed
• [Journal Article] Diacylglycerol Kinase &zeta; Inhibits Ventricular Tachyarrhythmias in a Mouse Model of Heart Failure (2011)
  • Author(s): Hirose, M., Takeishi, Y., Niizeki, T., Nakada, T., Shimojo, H., Kashihara, T., Horiuchi-Hirose, M., Kubota, I., Mende, U., Yamada, M
  • Journal Title: Circulation Journal Volume: 75 Issue: 10 Pages: 2333-2342
  • DOI: 10.1253/circj.CJ-10-1213
  • NAID: 10029459214
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Decrease in the density of t-tubular L-type Ca^<2+> channel currents in failing ventricular myocytes (2011)
  • Author(s): 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
  • Journal Title: Am.J.Physiol.Heart Circ.Physiol. Volume: 300
  • Peer Reviewed
• [Presentation] L型カルシウムチャネルとリアノジン受容体の結合膜局在化におけるジャンクトフィリンの役割 (2012)
  • Author(s): 中田勉, Bernhard E.Flucher, 柏原俊英, 生暁娜, 柴崎利英, 五味志文, 山田充彦
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-16
• [Presentation] Proximal C-terminus of alC subunits is necessary for junctional membrane-targeting of cardiac L-type calcium channels (2011)
  • Author(s): Tsutomu Nakada, Bernhard E.Flucher, Toshihide Kashihara, Xiaona Sheng, Toshihide Shibazaki, Miwa Horiuchi-Hirose, Masamichi Hirose, Mitsuhiko Yamada
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] 心筋L型カルシウムチャネルの結合膜局在化モチーフの探索 (2011)
  • Author(s): 中田勉, Bernhard E Flucher,生暁梛,柏原俊英,柴崎利英,山田充彦
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-16
• [Presentation] GLT細胞を用いた心筋L型Ca^<2+>チャネルのクラスタリング機構の解析 (2010)
  • Author(s): 中田勉, Bernhard E Flucher, 生暁娜, 柏原俊英, 柴崎利英, 山田充彦
  • Organizer: 第123回日本薬理学会関東部会
  • Place of Presentation: 栃木
  • Year and Date: 2010-10-23