Structural diversity of L-type Ca^<2+> channel in sinoatrial node-the possibility of Cav-Cav interaction-

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790199
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General physiology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: TOYODA Futoshi Shiga University of Medical Science, 医学部, 助教 (90324574)
• Project Period (FY): 2009 – 2010
• Keywords: 生体膜 / チャネル / トランスポーター / 能動輸送

Research Abstract

In the present study, we examined the possibility of the functional assembly of Cav1.2 and Cav1.3 subunits to yield the sustained inward Na^+ current (I_<st>), a pacemaker current in sinoatrial node. Heterologous coexpression of Cav1.2 and Cav1.3 in HEK cells resulted in an ensemble of Ca^<2+> currents attributed to each Cav channel. On the other hand, the chimeric channel consisting of repeat I and II from Cav1.2 (or Cav1.3) and repeat III and IV from Cav1.3 (or Cav1.2) elicited a rapidly inactivating Ca^<2+> current but failed to evoke a Na^+ current similar to I_<st>. Taken together, it is not likely that the heteromeric assembly of Cav1.2 and Cav1.3 subunits underlies I_<st> in sinoatrial node.

Research Products

• [Journal Article] Minor contribution of cytosolic Ca^<2+> transients to the pacemaker rhythm in guinea pig sinoatrial node cells. (2010)
  • Author(s): Himeno Y, Toyoda F, Satoh H, Amano A, Cha CY, Matsuura H, Noma A.
  • Journal Title: Am J Physiol. 300 Pages: H251-H261
  • Peer Reviewed
• [Journal Article] Lysophosphatidylcholine enhances I_<Ks> currents in cardiac myocytes through activation of G protein, PKC and Rho signaling pathways. (2010)
  • Author(s): Ding WG, Toyoda F, Ueyama H, Matsuura H.
  • Journal Title: J Mol Cell Cardiol. 50 Pages: 58-65
  • Peer Reviewed
• [Journal Article] Characterization of the rapidly activating delayed rectifier potassium current, I_<Kr>, in HL-1 mouse atrial myocytes. (2010)
  • Author(s): Toyoda F, Ding WG, Zankov PD, Omatsu-Kanbe M, Isono T, Horie M, Matsuura H.
  • Journal Title: J Memb Biol. 235 Pages: 73-87
  • Peer Reviewed
• [Journal Article] KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders. (2010)
  • Author(s): Wu J, Shimizu W, Ding WG, Ohno S, Toyoda F, Itoh H, Zang WJ, Miyamoto Y, Kamakura S, Matsuura H, Nademanee K, Brugada J, Brugada P, Brugada R, Vatta M, Towbin JA, Antzelevitch C, Horie M.
  • Journal Title: Heart Rhythm. 7 Pages: 199-205
  • Peer Reviewed
• [Journal Article] D85N, a KCNE1 polymorphism, is a disease-causing gene variant in long QT syndrome. (2009)
  • Author(s): Nishio Y, Makiyama T, Itoh H, Sakaguchi T, Ohno S, Gong YZ, Yamamoto S, Ozawa T, Ding WG, Toyoda F, Kawamura M, Akao M, Matsuura H, Kimura T, Kita T, Horie M.
  • Journal Title: J Am Coll Cardiol. 54 Pages: 812-819
  • Peer Reviewed
• [Journal Article] Regulatory role of tyrosine phosphorylation in the swelling-activated chloride current in isolated rabbit articular chondrocytes. (2009)
  • Author(s): Okumura N, Imai S, Toyoda F, Isoya E, Kumagai K, Matsuura H, Matsusue Y.
  • Journal Title: J Physiol. 587 Pages: 3761-3776
  • Peer Reviewed
• [Journal Article] Adrenergic regulation of the rapid component of delayed rectifier K^+ current:implications for arrhythmogenesis in LQT2 patients. (2009)
  • Author(s): Zankov DP, Yoshida H, Tsuji K, Toyoda F, Ding WG, Matsuura H, Horie M.
  • Journal Title: Heart Rhythm. 6 Pages: 1038-1046
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor mediates partially hyposmoticinduced increase of I_<Ks> current in guinea pig atrium. (2009)
  • Author(s): Zankov DP, Toyoda F, Omatsu-Kanbe M, Matsuura H, Horie M.
  • Journal Title: Pflugers Arch. 458 Pages: 837-849
  • Peer Reviewed
• [Journal Article] Dynamic partnership between KCNQ1 and KCNE1 and influence on cardiac IKs current amplitude by KCNE2. (2009)
  • Author(s): Jiang M, Xu X, Wang Y, Toyoda F, Liu XS, Zhang M, Robinson RB, Tseng GN.
  • Journal Title: J Biol Chem. 284 Pages: 16452-16462
  • Peer Reviewed
• [Journal Article] Novel KCNE3 mutation reduces repolarizing potassium current and associatedwith long QT syndrome. (2009)
  • Author(s): Ohno S, Toyoda F, Zankov DP, Yoshida H, Makiyama T, Tsuji K, Honda T, Obayashi K, Ueyama H, Shimizu W, Miyamoto Y, Kamakura S, Matsuura H, Kita T, Horie M.
  • Journal Title: Hum Mutat. 30 Pages: 557-563
  • Peer Reviewed
• [Presentation] A sodium-permeable CaV1.3 mutant channel exhibts electrophysiological properties characteristics of the sustained inward current in sinoatrial node cells. (2010)
  • Author(s): Toyoda F, Ding WG, Matsuura H.
  • Organizer: 第87回日本生理学会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-19
• [Presentation] Generation of sodium-permeable CaV1.3 channel : insights into the molecular basis for the sustained inward current in cardiac pacemaker cells. (2010)
  • Author(s): Toyoda F, Ding WG, Matsuura H.
  • Organizer: Biophysical Society 54^<th> Annual Meeting.
  • Place of Presentation: 米国サ ンフランシスコ
  • Year and Date: 2010-02-22
• [Presentation] The role of KCNE3 in the regulation of cardiac KCNQ1 potassium channel. (2009)
  • Author(s): Toyoda F, Ding WG, Matsuura H.
  • Organizer: 36^<th> International Congress of Physiological Science.
  • Place of Presentation: 京都
  • Year and Date: 2009-07-28
• [Presentation] NaA^+透過性CaV1.3チャネルの作製-I_<st>の分子基盤の解明を目指して- (2009)
  • Author(s): 豊田太・丁維光・松浦博
  • Organizer: 日本心電学会
  • Place of Presentation: 京都
  • Year and Date: 2009-07-03