Release of Ca²⁺ from the sarcoplasmic reticulum (SR) in cardiomyocytes occurs at functional units where Ca²⁺ channels located in the t-tubules face SR Ca²⁺ release channels. The close proximity of these proteins ensure efficient excitation-contraction coupling. Experimentally reducing t-tubule density has been shown to increase the dyssynchrony of Ca²⁺ release (Louch et al. 2004). We investigated whether alterations in t-tubule density and Ca²⁺ release synchrony occur in cardiomyocytes from rats with post infarction congestive heart failure (CHF). Post infarction CHF was induced by ligation of the left coronary artery. Hearts were fixed with a solution containing 4% paraformaldehyde and mounted in Lowicryl HM20 resin. Thin sections were cut, mounted onto nickel grids, and randomized for blinded examination by electron microscopy. Mean density of the t-tubules was lower in micrographs from failing cardiomyocytes compared to sham (21 ± 2 t-tubules/100 mm² vs. 36 ± 2 t-tubules/100 mm², p < 0.01). T-tubule density was also reduced in live cardiomyocytes labeled with Alexa 488 conjugated wheat germ agglutine (WGA). Line-scan images of Ca²⁺ transients (fluo-4 AM, 1Hz) in field stimulated isolated cardiomyocytes showed that SR Ca²⁺ release was significantly less synchronous in failing than in sham cells. The degree of dyssynchrony correlated with the severity of CHF. Thus, loss of t-tubules during CHF development may promote dyssynchrony of Ca²⁺ release, and contribute to decreased efficiency of excitation-contraction coupling in this disease.

Louch, W.E., Bito V., Heinzel F.R., Macianskiene R., Vanhaecke J., Flameng W., Mubagwa K. & Sipido K.R. 2004. Cardiovasc Res 62, 63-73.