title: Remodeling of T-tubules and reduced synchrony of Ca2+ release in myocytes from chronically ischemic myocardium.
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-amino-naphthyl-ethylene-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.
authors: Division of Experimental Cardiology, University Hospital Gasthuisberg and University of Leuven, Belgium.
authors: Frank R
authors: FR
authors: Heinzel
authors: Virginie
authors: V
authors: Bito
authors: Liesbeth
authors: L
authors: Biesmans
authors: Ming
authors: M
authors: Wu
authors: Elke
authors: E
authors: Detre
authors: Frederik
authors: F
authors: von Wegner
authors: Piet
authors: P
authors: Claus
authors: Steven
authors: S
authors: Dymarkowski
authors: Frederik
authors: F
authors: Maes
authors: Jan
authors: J
authors: Bogaert
authors: Frank
authors: F
authors: Rademakers
authors: Jan
authors: J
authors: D'hooge
authors: Karin
authors: K
authors: Sipido
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D023921:Coronary Stenosis / Q000378:metabolism / Q000473:pathology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D034421:Sus scrofa; D013997:Time Factors
chemical_list: C089669:1-(3-sulfonatopropyl)-4-(beta-(2-(di-n-octylamino)-6-naphthyl)vinyl)pyridinium betaine; D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium