SARCOPLASMIC RETICULUM-RELATED CHANGES IN CYTOSOLIC CALCIUM IN PRESSURE-OVERLOAD-INDUCED FELINE LV HYPERTROPHY

Alterations in Ca2+ homeostasis that involve the sarcoplasmic reticulu m (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 hear t weight-to-body weight ratio (8.4 +/- 0.6 vs. 4.2 +/- 0.2 g/kg in con trols). Steady-state Ca2+ transients (measured as indo 1 fluorescence at 410 nm/480 nm; I410/I480) in LV hypertrophy (LVH) myocytes had dimi nished peak amplitudes (I410/I480 2.28 +/- 0.07 vs. 2.53 +/- 0.07 in c ontrols) and prolonged durations (0.75 +/- 0.03 vs. 0.59 +/- 0.02 s in controls). The magnitude of shortening was reduced and the contractil e duration was prolonged in LVH myocytes. The idea that changes in SR function are responsible for these alterations in the Ca2+ transient w as tested by studying two aspects of SR-related Ca2+ homeostasis. Rest itution of releasable SR Ca2+ was studied by measuring indo 1 transien ts and contractions during premature beats. The time course of restitu tion of both the indo 1 transient and contraction of hypertrophy myocy tes 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 followi ng long rest periods (rest decay) was measured to determine the rate o f 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. These studies support the idea t hat changes in the function of the SR alters the Ca2+ transient and ma y produce the contractile disturbances of the hypertrophied feline myo cyte.