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Sarcoplasmic reticulum-related changes in cytosolic calcium in pressure-overload-induced feline LV hypertrophy
1Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Insights
In feline hearts with left ventricular hypertrophy (LVH), sarcoplasmic reticulum (SR) calcium (Ca2+) handling is impaired. SR Ca2+ release is slowed, and Ca2+ leak from the SR is accelerated in LVH.
Area of Science:
- Cardiology
- Cell Physiology
- Biochemistry
Background:
- Left ventricular hypertrophy (LVH) is a cardiac condition often associated with impaired contractility.
- Sarcoplasmic reticulum (SR) Ca2+ handling is critical for cardiomyocyte function.
- Previous studies suggest alterations in SR Ca2+ homeostasis contribute to contractile dysfunction in heart disease.
Purpose of the Study:
- To investigate alterations in sarcoplasmic reticulum (SR) Ca2+ homeostasis in feline left ventricular (LV) myocytes with hypertrophy.
- To determine the impact of LV hypertrophy on SR Ca2+ release and reuptake dynamics.
Main Methods:
- Isolation of feline left ventricular (LV) myocytes from control and hypertrophied hearts (induced by pressure overload).
- Measurement of steady-state Ca2+ transients using indo 1 fluorescence.
- Assessment of SR Ca2+ restitution and Ca2+ leak during premature beats and post-rest periods.
Main Results:
- LV hypertrophy myocytes exhibited diminished peak Ca2+ transient amplitudes and prolonged durations.
- The restitution of releasable SR Ca2+ was significantly slower in LVH myocytes compared to controls.
- Accelerated Ca2+ loss from the SR (increased rest decay) was observed in LVH myocytes.
Conclusions:
- Altered SR Ca2+ handling, specifically slowed Ca2+ release and accelerated Ca2+ leak, contributes to impaired Ca2+ transients and contractile dysfunction in feline LV hypertrophy.
- These findings highlight the SR as a key player in the pathophysiology of pressure-overload induced cardiac hypertrophy.
Abstract:
Alterations in Ca2+ homeostasis that involve the sarcoplasmic reticulum (SR) were studied in feline left ventricular (LV) myocytes isolated from hearts with LV hypertrophy induced by slow, progressive pressure overload. At death, severe hypertrophy was evidenced by increased heart weight-to-body weight ratio (8.4 +/- 0.6 vs. 4.2 +/- 0.2 g/kg in controls). Steady-state Ca2+ transients (measured as. indo 1 fluorescence at 410 nm/480 nm; I410/I480) in LV hypertrophy (LVH) myocytes had diminished peak amplitudes (I410/I480 2.28 +/- 0.07 vs. 2.53 +/- 0.07 in controls) and prolonged durations (0.75 +/- 0.03 vs. 0.59 +/- 0.02 s in controls). The magnitude of shortening was reduced and the contractile duration was prolonged in LVH myocytes. The idea that changes in SR function are responsible for these alterations in the Ca2+ transient was tested by studying two aspects of SR-related Ca2+ homeostasis. Restitution of releasable SR Ca2+ was studied by measuring indo 1 transients and contractions during premature beats. The time course of restitution of both the indo 1 transient and contraction of hypertrophy myocytes was significantly slower than in controls. These data suggest that restitution of releasable SR Ca2+ is slowed in hypertrophy myocytes. The reduction of the indo 1 transient and contraction in beats following long rest periods (rest decay) was measured to determine the rate of Ca2+ loss from the SR. Rest decay was significantly (P < 0.05) more pronounced in hypertrophy myocytes, suggesting that Ca2+ loss from the SR is accelerated in these myocytes. (ABSTRACT TRUNCATED AT 250 WORDS)