AJP - Heart Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 284: H1035-H1042, 2003. First published November 14, 2002; doi:10.1152/ajpheart.00722.2002
0363-6135/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/3/H1035    most recent
00722.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (36)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kohno, M.
Right arrow Articles by Matsuzaki, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kohno, M.
Right arrow Articles by Matsuzaki, M.
Vol. 284, Issue 3, H1035-H1042, March 2003

A new cardioprotective agent, JTV519, improves defective channel gating of ryanodine receptor in heart failure

Masateru Kohno, Masafumi Yano, Shigeki Kobayashi, Masahiro Doi, Tetsuro Oda, Takahiro Tokuhisa, Shinichi Okuda, Tomoko Ohkusa, Michihiro Kohno, and Masunori Matsuzaki

Department of Medical Bioregulation, Division of Cardiovascular Medicine, Yamaguchi University School of Medicine, Yamaguchi 755-8505, Japan

Defective interaction between FKBP12.6 and ryanodine receptors (RyR) is a possible cause of cardiac dysfunction in heart failure (HF). Here, we assess whether the new cardioprotective agent JTV519 can correct it in tachycardia-induced HF. HF was induced in dogs by 4-wk rapid ventricular pacing, and sarcoplasmic reticulum (SR) was isolated from left ventricular muscles. In failing SR, JTV519 increased the rate of Ca2+ release and [3H]ryanodine binding. RyR were then labeled in a site-directed fashion with the fluorescent conformational probe methylcoumarin acetamide. In failing SR, the polylysine induced a rapid change in methylcoumarin acetamide fluorescence, presumably because the channel opening preceding the Ca2+ release was smaller than in normal SR (consistent with a decreased rate of Ca2+ release in failing SR), and JTV519 increased it. In conclusion, JTV519, a new 1,4-benzothiazepine derivative, corrected the defective channel gating in RyR (increase in both the rapid conformational change and the subsequent Ca2+ release rate) in HF.

sarcoplasmic reticulum; ion channel; binding protein; excitation-contraction coupling


This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
C.M. Loughrey, N. Otani, T. Seidler, M.A. Craig, R. Matsuda, N. Kaneko, and G.L. Smith
K201 modulates excitation-contraction coupling and spontaneous Ca2+ release in normal adult rabbit ventricular cardiomyocytes
Cardiovasc Res, November 1, 2007; 76(2): 236 - 246.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
S. A. Goonasekera, S. R. W. Chen, and R. T. Dirksen
Reconstitution of local Ca2+ signaling between cardiac L-type Ca2+ channels and ryanodine receptors: insights into regulation by FKBP12.6
Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1476 - C1484.
[Abstract] [Full Text] [PDF]

Home page
 Mayo Clin Proc.Home page
X. H. T. Wehrens and A. R. Marks
Sudden Unexplained Death Caused by Cardiac Ryanodine Receptor (RyR2) Mutations
Mayo Clin. Proc., November 1, 2004; 79(11): 1367 - 1371.
[PDF]

Home page
 CirculationHome page
S. E. Lehnart, X. H.T. Wehrens, P. J. Laitinen, S. R. Reiken, S.-X. Deng, Z. Cheng, D. W. Landry, K. Kontula, H. Swan, and A. R. Marks
Sudden Death in Familial Polymorphic Ventricular Tachycardia Associated With Calcium Release Channel (Ryanodine Receptor) Leak
Circulation, June 29, 2004; 109(25): 3208 - 3214.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online