© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Depletion of T-tubules and specific subcellular changes in sarcolemmal proteins in tachycardia-induced heart failure
aDepartment of Medicine, University of Wisconsin, Madison, WI, USA
bDepartment of Physiology, University of Wisconsin, Madison, WI, USA
cDepartment of Surgery, University of Wisconsin, Madison, WI, USA
tjk{at}medicine.wisc.edu
* Corresponding author. H6/343 Clinical Science Center, Box 3248, 600 Highland Ave., Madison, WI 53792, USA. Tel.: +1-608-263-4856; fax: +1-608-263-0405.
Objective: The T-tubule membrane network is integrally involved in excitation–contraction coupling in ventricular myocytes. Ventricular myocytes from canine hearts with tachycardia-induced dilated cardiomyopathy exhibit a decrease in accessible T-tubules to the membrane-impermeant dye, di8-ANNEPs. The present study investigated the mechanism of loss of T-tubule staining and examined for changes in the subcellular distribution of membrane proteins essential for excitation–contraction coupling. Methods: Isolated ventricular myocytes from canine hearts with and without tachycardia-induced heart failure were studied using fluorescence confocal microscopy and membrane fractionation techniques using a variety of markers specific for sarcolemmal and sarcoplasmic reticulum proteins. Results: Probes for surface glycoproteins, Na/K ATPase, Na/Ca exchanger and Cav1.2 demonstrated a prominent but heterogeneous reduction in T-tubule labeling in both intact and permeabilised failing myocytes, indicating a true depletion of T-tubules and associated membrane proteins. Membrane fractionation studies showed reductions in L-type Ca2+ channels and β-adrenergic receptors but increased levels of Na/Ca exchanger protein in both surface sarcolemma and T-tubular sarcolemma-enriched fractions; however, the membrane fraction enriched in junctional complexes of sarcolemma and junctional sarcoplasmic reticulum demonstrated no significant changes in the density of any sarcolemmal protein or sarcoplasmic reticulum protein assayed. Conclusion: Failing canine ventricular myocytes exhibit prominent depletion of T-tubules and changes in the density of a variety of proteins in both surface and T-tubular sarcolemma but with preservation of the protein composition of junctional complexes. This subcellular remodeling contributes to abnormal excitation–contraction coupling in heart failure.
KEYWORDS Ca-channel; E-c coupling; Heart failure; Remodeling; Sarcolemma
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. M. Dibb, J. D. Clarke, M. A. Horn, M. A. Richards, H. K. Graham, D. A. Eisner, and A. W. Trafford Characterization of an Extensive Transverse Tubular Network in Sheep Atrial Myocytes and its Depletion in Heart Failure Circ Heart Fail, September 1, 2009; 2(5): 482 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hirose, B. D. Stuyvers, W. Dun, H. E.D.J. ter Keurs, and P. A. Boyden Function of Ca2+ Release Channels in Purkinje Cells That Survive in the Infarcted Canine Heart: A Mechanism for Triggered Purkinje Ectopy Circ Arrhythm Electrophysiol, December 1, 2008; 1(5): 387 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cheng and W. J. Lederer Calcium Sparks Physiol Rev, October 1, 2008; 88(4): 1491 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Y. Chung, M. Kang, and J. W. Walker Contractile regulation by overexpressed ETA requires intact T tubules in adult rat ventricular myocytes Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2391 - H2399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Swift, J. A. K. Birkeland, N. Tovsrud, U. H. Enger, J. M. Aronsen, W. E. Louch, I. Sjaastad, and O. M. Sejersted Altered Na+/Ca2+-exchanger activity due to downregulation of Na+/K+-ATPase {alpha}2-isoform in heart failure Cardiovasc Res, April 1, 2008; 78(1): 71 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Orchard and F. Brette t-tubules and sarcoplasmic reticulum function in cardiac ventricular myocytes Cardiovasc Res, January 15, 2008; 77(2): 237 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Bito, F. R. Heinzel, L. Biesmans, G. Antoons, and K. R. Sipido Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling Cardiovasc Res, January 15, 2008; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Lehnart, M. J. Ackerman, D. W. Benson Jr, R. Brugada, C. E. Clancy, J. K. Donahue, A. L. George Jr, A. O. Grant, S. C. Groft, C. T. January, et al. Inherited Arrhythmias: A National Heart, Lung, and Blood Institute and Office of Rare Diseases Workshop Consensus Report About the Diagnosis, Phenotyping, Molecular Mechanisms, and Therapeutic Approaches for Primary Cardiomyopathies of Gene Mutations Affecting Ion Channel Function Circulation, November 13, 2007; 116(20): 2325 - 2345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Brette and C. Orchard Resurgence of Cardiac T-Tubule Research Physiology, June 1, 2007; 22(3): 167 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kang, K. Y. Chung, and J. W. Walker G-Protein Coupled Receptor Signaling in Myocardium: Not for the Faint of Heart Physiology, June 1, 2007; 22(3): 174 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Y. Chung and J. W. Walker Interaction and Inhibitory Cross-Talk between Endothelin and ErbB Receptors in the Adult Heart Mol. Pharmacol., June 1, 2007; 71(6): 1494 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Armoundas, J. Rose, R. Aggarwal, B. D. Stuyvers, B. O'Rourke, D. A. Kass, E. Marban, S. R. Shorofsky, G. F. Tomaselli, and C. William Balke Cellular and molecular determinants of altered Ca2+ handling in the failing rabbit heart: primary defects in SR Ca2+ uptake and release mechanisms Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1607 - H1618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Bootman, D. R. Higazi, S. Coombes, and H. L. Roderick Calcium signalling during excitation-contraction coupling in mammalian atrial myocytes. J. Cell Sci., October 1, 2006; 119(Pt 19): 3915 - 3925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. Louch, H. K. Mork, J. Sexton, T. A. Stromme, P. Laake, I. Sjaastad, and O. M. Sejersted T-tubule disorganization and reduced synchrony of Ca2+ release in murine cardiomyocytes following myocardial infarction J. Physiol., July 15, 2006; 574(2): 519 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Balijepalli, J. D. Foell, D. D. Hall, J. W. Hell, and T. J. Kamp From the Cover: Localization of cardiac L-type Ca2+ channels to a caveolar macromolecular signaling complex is required for beta2-adrenergic regulation PNAS, May 9, 2006; 103(19): 7500 - 7505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-S. Song, E. A. Sobie, S. McCulle, W. J. Lederer, C. W. Balke, and H. Cheng Orphaned ryanodine receptors in the failing heart. PNAS, March 14, 2006; 103(11): 4305 - 4310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido and D. Eisner Something old, something new: Changing views on the cellular mechanisms of heart failure Cardiovasc Res, November 1, 2005; 68(2): 167 - 174. [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Q. He, R. C. Balijepalli, R. A. Haworth, and T. J. Kamp Crosstalk of {beta}-Adrenergic Receptor Subtypes Through Gi Blunts {beta}-Adrenergic Stimulation of L-Type Ca2+ Channels in Canine Heart Failure Circ. Res., September 16, 2005; 97(6): 566 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-S. Song, Y. Pi, S.-J. Kim, A. Yatani, S. Guatimosim, R. K. Kudej, Q. Zhang, H. Cheng, L. Hittinger, B. Ghaleh, et al. Paradoxical Cellular Ca2+ Signaling in Severe but Compensated Canine Left Ventricular Hypertrophy Circ. Res., September 2, 2005; 97(5): 457 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Viatchenko-Karpinski, D. Terentyev, L. A. Jenkins, L. O. Lutherer, and S. Gyorke Synergistic interactions between Ca2+ entries through L-type Ca2+ channels and Na+-Ca2+ exchanger in normal and failing rat heart J. Physiol., September 1, 2005; 567(2): 493 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Cohen, J. D. Foell, R. C. Balijepalli, V. Shah, J. W. Hell, and T. J. Kamp Unique modulation of L-type Ca2+ channels by short auxiliary {beta}1d subunit present in cardiac muscle Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2363 - H2374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Fowler, J. R. Naz, M. D. Graham, G. Bru-Mercier, S. M. Harrison, and C. H. Orchard Decreased Ca2+ extrusion via Na+/Ca2+ exchange in epicardial left ventricular myocytes during compensated hypertrophy Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2431 - H2438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kiarash, C. E Kelly, B. S Phinney, H. H Valdivia, J. Abrams, and S. E Cala Defective glycosylation of calsequestrin in heart failure Cardiovasc Res, August 1, 2004; 63(2): 264 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R Fowler, R. S Dobson, C. H Orchard, and S. M Harrison Functional consequences of detubulation of isolated rat ventricular myocytes Cardiovasc Res, June 1, 2004; 62(3): 529 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Foell, R. C. Balijepalli, B. P. Delisle, A. M. R. Yunker, S. L. Robia, J. W. Walker, M. W. McEnery, C. T. January, and T. J. Kamp Molecular heterogeneity of calcium channel {beta}-subunits in canine and human heart: evidence for differential subcellular localization Physiol Genomics, April 13, 2004; 17(2): 183 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hatem Does the loss of transverse tubules contribute to dyssynchronous Ca2+ release during heart failure? Cardiovasc Res, April 1, 2004; 62(1): 1 - 3. [Full Text] [PDF]
|
|
|
|
|
|
W. E Louch, V. Bito, F. R Heinzel, R. Macianskiene, J. Vanhaecke, W. Flameng, K. Mubagwa, and K. R Sipido Reduced synchrony of Ca2+ release with loss of T-tubules--a comparison to Ca2+ release in human failing cardiomyocytes Cardiovasc Res, April 1, 2004; 62(1): 63 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido Understanding Cardiac Alternans: The Answer Lies in the Ca2+ Store Circ. Res., March 19, 2004; 94(5): 570 - 572. [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. Robu, E. S. Pfeiffer, S. L. Robia, R. C. Balijepalli, Y. Pi, T. J. Kamp, and J. W. Walker Localization of Functional Endothelin Receptor Signaling Complexes in Cardiac Transverse Tubules J. Biol. Chem., November 28, 2003; 278(48): 48154 - 48161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F R Quinn, S Currie, A M Duncan, S Miller, R Sayeed, S M Cobbe, and G L Smith Myocardial infarction causes increased expression but decreased activity of the myocardial Na+--Ca2+ exchanger in the rabbit J. Physiol., November 15, 2003; 553(1): 229 - 242. [Abstract] [Full Text] [PDF]
|
|