Reduced synchrony of Ca$^2+$ release with loss of T-tubules-a
comparison to Ca$^2+$ release in human failing cardiomyocytes.
Cardiovasc. Res., 62 (1):
63--73 (April 2004)DOI: 10.1016/j.cardiores.2003.12.031
Abstract
OBJECTIVES: During cardiac excitation-contraction coupling, Ca$^2+$
release from the sarcoplasmic reticulum (SR) occurs at the junctional
complex with the T-tubules, containing the L-type Ca$^2+$ 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 Ca$^2+$ release. METHODS:
Adult pig ventricular myocytes were isolated and cultured for 24
and 72 h. T-tubules, visualized with di-8-ANEPPS, and Ca$^2+$i
transients (Fluo-3) were recorded during confocal line scan imaging.
RESULTS: Cultured cardiomyocytes exhibited a progressive reduction
in T-tubule density. Ca$^2+$i transients showed small areas
of delayed Ca$^2+$ release which gradually increased in number
and size with loss of T-tubules. Local Ca$^2+$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 Ca$^2+$
along the entire line scan and transient magnitude tended to be reduced,
but there was no change in SR Ca$^2+$ 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 Ca$^2+$i was significantly faster than in pig myocytes
with low T-tubule density. CONCLUSIONS: Loss of T-tubules reduces
the synchrony of SR Ca$^2+$ release. This could contribute to
reduced efficiency of excitation-contraction coupling in heart failure,
though dyssynchrony in human failing cells appears to be modest.
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