Reduced synchrony of Ca2+ release with loss of T-tubules: a comparison to Ca2+ release in human failing cardiomyocytes

• Published in: Cardiovascular research 2004-04, Vol.62 (1), p.63-73
• Main Authors: LOUCHA, William E, BITO, Virginie, HEINZEL, Frank R, MACIANSKIENE, Regina, VANHAECKEA, Johan, FLAMENG, Willem, MUBAGWA, Kanigula, SIPIDO, Karin R
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cardiology. Vascular system; Cells, Cultured; Electrophysiology; Heart; Heart Failure - metabolism; Heart Failure - pathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Image Processing, Computer-Assisted; Medical sciences; Microscopy, Confocal; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Sarcoplasmic Reticulum - ultrastructure; Swine
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2003.12.031

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. 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. 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. 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.