© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Reduced synchrony of Ca2+ release with loss of T-tubules—a comparison to Ca2+ release in human failing cardiomyocytes
aLaboratory of Experimental Cardiology, University of Leuven, Campus Gasthuisberg O/N 7th floor, Herestraat 49, B-3000 Leuven, Belgium
bInstitute of Pathophysiology, University of Essen, Essen, Germany
cCenter for Experimental Surgery, University of Leuven, Leuven, Belgium
* Corresponding author. Tel.: +32-16-347153; fax: +32-16-345844. Email address: karin.sipido{at}med.kuleuven.ac.be
Objectives: During cardiac excitation–contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at the junctional complex with the T-tubules, containing the L-type Ca2+ channels. A partial loss of T-tubules has been described in myocytes from failing canine and human hearts. We examined how graded reduction of T-tubule density would affect the synchrony of Ca2+ release. Methods: Adult pig ventricular myocytes were isolated and cultured for 24 and 72 h. T-tubules, visualized with di-8-ANEPPS, and [Ca2+]i transients (Fluo-3) were recorded during confocal line scan imaging. Results: Cultured cardiomyocytes exhibited a progressive reduction in T-tubule density. [Ca2+]i transients showed small areas of delayed Ca2+ release which gradually increased in number and size with loss of T-tubules. Local [Ca2+]i transients in the delayed regions were reduced. Due to these changes, loss of T-tubules resulted in an overall slowing of the rise of [Ca2+] along the entire line scan and transient magnitude tended to be reduced, but there was no change in SR Ca2+ content. Human myocytes isolated from failing hearts had a T-tubule density comparable to that of freshly isolated pig myocytes. The size, but not the number, of delayed release areas tended to be larger. The overall rate of rise of [Ca2+]i was significantly faster than in pig myocytes with low T-tubule density. Conclusions: Loss of T-tubules reduces the synchrony of SR Ca2+ release. This could contribute to reduced efficiency of excitation–contraction coupling in heart failure, though dyssynchrony in human failing cells appears to be modest.
KEYWORDS Heart failure; Calcium; Cell culture; E–C coupling; Myocytes; SR (function); Sarcolemma; T-tubules; Pig; Confocal microscopy
Time for primary review 20 days
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