In hypertrophic rat hearts induced by aortic banding, unloaded myocyte contraction was depressed, and reduction of extracellular Ca to 0.5 mM unmasked a depressed fractional SR Ca release.
In a rat model of left ventricular hypertrophy, unloaded myocyte contraction is depressed and fractional SR Ca release is impaired under reduced extracellular calcium conditions.
Left ventricular hypertrophy (approximately 40%) was induced in rats by banding of the abdominal aorta. After 16 wk, ventricular homogenates were prepared for biochemical measurements and ventricular myocytes were isolated for functional studies. In myocytes, the effects of banding on intracellular Ca handling, contraction, and excitation-contraction (E-C) coupling were determined using indo 1 fluorescence and whole cell voltage clamp. After steady-state field or voltage-clamp stimulation to load the sarcoplasmic reticulum (SR), SR Ca content assessed by caffeine-induced Ca transients was the same in sham and banded groups. Despite this, cell shortening amplitudes were significantly depressed in the banded group, suggesting altered contractile properties. In banded rats, the SR Ca-adenosinetriphosphatase (Ca-ATPase) mRNA level was reduced, as was homogenate thapsigargin-sensitive SR Ca-ATPase, but cytosolic free Ca concentration (Cai) decline attributed to SR Ca-ATPase activity in intact cells was not slowed. Banding also reduced Na/Ca exchange mRNA level but did not affect either Na-dependent sarcolemmal 45Ca transport in homogenate or the rate of Cai decline in intact cells attributed to Na/Ca exchange (during caffeine-induced contractures). Banding also did not change the rate of Cai decline mediated by the combined function of the mitochondrial Ca uptake and sarcolemmal Ca-ATPase in intact cells. Ca current (ICa) density and voltage dependence were the same in sham and banded groups. Ryanodine receptor mRNA, protein content, and ryanodine affinity were also unchanged in the banded group. At 1 mM extracellular Ca concentration (Cao), banding did not affect E-C coupling efficacy in intact cells under voltage clamp (i.e., same contraction for given ICa and SR Ca load). However, when Cao was reduced to 0.5 mM, the efficacy of E-C coupling was greatly depressed in the banded group (even though ICa and SR Ca content were matched). In summary, unloaded myocyte contraction was depressed in these hypertrophic hearts, but Ca transport was little altered, at 1 mM Cao. However, reduction of Cao to 0.5 mM appears to unmask a depressed fractional SR Ca release in response to a given ICa trigger and SR Ca load.
McCall et al. (Wed,) conducted a other in Left ventricular hypertrophy. Abdominal aorta banding vs. Sham was evaluated on Ca flux, contractility, and excitation-contraction coupling. In hypertrophic rat hearts induced by aortic banding, unloaded myocyte contraction was depressed, and reduction of extracellular Ca to 0.5 mM unmasked a depressed fractional SR Ca release.