Title: Remodeling of T-tubules and reduced synchrony of Ca2+ release in myocytes from chronically ischemic myocardium
Authors: Heinzel, Frank R
Bito, Virginie
Biesmans, Liesbeth
Wu, Ming
Detré, Elke
von Wegner, Frederik
Claus, Piet
Dymarkowski, Steven
Maes, Frederik
Bogaert, Jan
Rademakers, Frank
D'hooge, Jan
Sipido, Karin # ×
Issue Date: Feb-2008
Publisher: Lippincott williams & wilkins
Series Title: Circulation Research vol:102 issue:3 pages:338-346
Abstract: In ventricular cardiac myocytes, T-tubule density is an important determinant of the synchrony of sarcoplasmic reticulum (SR) Ca2+ release and could be involved in the reduced SR Ca2+ release in ischemic cardiomyopathy. We therefore investigated T-tubule density and properties of SR Ca2+ release in pigs, 6 weeks after inducing severe stenosis of the circumflex coronary artery (91 +/- 3%, N = 13) with myocardial infarction (8.8 +/- 2.0% of total left ventricular mass). Severe dysfunction in the infarct and adjacent myocardium was documented by magnetic resonance and Doppler myocardial velocity imaging. Myocytes isolated from the adjacent myocardium were compared with myocytes from the same region in weight-matched control pigs. T-tubule density quantified from the di-8-ANEPPS (di-8-butyl-aminonaphthylethylene- pyridinium-propyl-sulfonate) sarcolemmal staining was decreased by 27 +/- 7% ( P < 0.05). Synchrony of SR Ca2+ release (confocal line scan images during whole-cell voltage clamp) was reduced in myocardium myocytes. Delayed release (ie, half-maximal [Ca2+](i) occurring later than 20 ms) occurred at 35.5 +/- 6.4% of the scan line in myocardial infarction versus 22.7 +/- 2.5% in control pigs (P < 0.05), prolonging the time to peak of the line-averaged [Ca2+](i) transient (121 +/- 9 versus 102 +/- 5 ms in control pigs, P < 0.05). Delayed release colocalized with regions of T-tubule rarefaction and could not be suppressed by activation of protein kinase A. The whole-cell averaged [Ca2+] i transient amplitude was reduced, whereas L-type Ca2+ current density was unchanged and SR content was increased, indicating a reduction in the gain of Ca2+-induced Ca2+ release. In conclusion, reduced T-tubule density during ischemic remodeling is associated with reduced synchrony of Ca2+ release and reduced efficiency of coupling Ca2+ influx to Ca2+ release.
Description: Heinzel F.R., Bito V., Biesmans L., Wu M., Detre E., von Wegner F., Claus P., Dymarkowski S., Maes F., Bogaert J., Rademakers F., D’hooge J., Sipido K., ''Remodeling of T-tubules and reduced synchrony of Ca2+ release in myocytes from chronically ischemic myocardium'', Circulation research, vol. 102, no. 3, pp. 338-346, 2008.
ISSN: 0009-7330
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Experimental Cardiology
Cardiovascular Imaging and Dynamics
ESAT - PSI, Processing Speech and Images
Translational MRI (+)
× corresponding author
# (joint) last author

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