Reduction in density of transverse tubules and L-type Ca(2+) channels in canine tachycardia-induced heart failure

Persistent supraventricular tachycardia leads to the development of a dilated cardiomyopathy with impairment of excitation-contraction (EC) coupling. Since the initial trigger for EC coupling in ventricular muscle is the influx of Ca(2+) through L-type Ca(2+) channels (I(Ca)) in the transverse tubul...

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Bibliographic Details
Published in:Cardiovascular research 2001-02, Vol.49 (2), p.298-307
Main Authors: He, J, Conklin, M W, Foell, J D, Wolff, M R, Haworth, R A, Coronado, R, Kamp, T J
Format: Article
Language:English
Subjects:
Adrenergic beta-Agonists - pharmacology
Animals
Calcium Channel Blockers - pharmacology
Calcium Channels, L-Type - metabolism
Cell Size
Dihydropyridines - pharmacology
Dogs
Heart Failure - etiology
Heart Failure - pathology
Heart Failure - physiopathology
Image Processing, Computer-Assisted
Ion Channel Gating - drug effects
Isoproterenol - pharmacology
Microscopy, Confocal
Models, Animal
Myocardium - metabolism
Myocardium - ultrastructure
Patch-Clamp Techniques
Tachycardia - complications
Tachycardia - pathology
Tachycardia - physiopathology
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Summary:Persistent supraventricular tachycardia leads to the development of a dilated cardiomyopathy with impairment of excitation-contraction (EC) coupling. Since the initial trigger for EC coupling in ventricular muscle is the influx of Ca(2+) through L-type Ca(2+) channels (I(Ca)) in the transverse tubules (T-tubules), we determined if the density of the T-tubule system and L-type Ca(2+) channels change in canine tachycardia pacing-induced cardiomyopathy. Confocal imaging of isolated ventricular myocytes stained with the membrane dye Di-8-ANEPPS was used to image the T-tubule system, and standard whole-cell patch clamp techniques were used to measure I(Ca) and intramembrane charge movement. A complex staining pattern of interconnected tubules including prominent transverse components spaced every approximately 1.6 microm was present in control ventricular myocytes, but failing cells demonstrated a far less regular T-tubule system with a relative loss of T-tubules. In confocal optical slices, the average % of the total cell area staining for T-tubules decreased from 11.5+/-0.4 in control to 8.7+/-0.4% in failing cells (P
ISSN:0008-6363
DOI:10.1016/S0008-6363(00)00256-X