Skip to main content
ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #117739


item Saari, Jack
item REN, JUN

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/9/2001
Publication Date: 8/1/2001
Citation: Wold, L.E., Saari, J.T., Ren, J. 2001. Isolated ventricular myocytes from copper-deficient rat hearts exhibit enhanced contractile function. American Journal of Physiology. 281:H476-H481.

Interpretive Summary: Prior studies have shown that dietary copper deficiency causes a variety of structural changes in the heart as well as impairment of the heart's electrical and contractile function. Previous measurements of reduced heart contraction in copper deficiency have been made in whole hearts. Because contraction of the whole heart may be influenced not only by contracting heart cells, but by the connective tissue holding them together, this study was done to determine how copper deficiency influences the contraction of isolated heart cells. Individual heart cells from copper-deficient and copper-adequate rats were separated, placed under a microscope and stimulated to contract. Cells from copper- deficient rats shortened more rapidly and to a greater degree than those from copper-adequate rats. Movement of calcium, which triggers contraction, was faster in copper-deficient than in copper-adequate cells. This apparently better contraction in individual copper-deficient cells contrasts with the reduced performance of the copper-deficient heart as a whole and might be a compensation for damage to other parts of the heart. Such studies will help scientists and consumers understand the importance of adequate copper nutrition to heart function.

Technical Abstract: Dietary copper deficiency leads to cardiac hypertrophy, cardiac fibrosis, derangement of myofibrils and impaired cardiac contractile and electrophysiological function. The purpose of the present study was to determine if the impaired cardiac function in copper deficiency is due to depressed contractile function at the single myocyte level. Male Sprague- Dawley rats were fed diets that were either copper-adequate (6.3 mg Cu/g) or copper-deficient (0.4 mg Cu/g) for 5 weeks. Ventricular myocytes were dispersed and mechanical properties were evaluated using the SoftEdge video-based edge-detection system. Intracellular Ca**2+ transients were examined using fura-2/AM. Nitric oxide synthase activity was inferred from the conversion of 3**H-arginine to 3H**-citrulline. Myocytes were electrically stimulated to contract at 0.5 Hz. Properties evaluated included peak shortening (PS), time-to-peak shortening (TPS) and time-to- 90% relengthening (TR**90), and maximal velocities of shortening and relengthening (+/- dL/dt). Myocytes from the copper-deficient rat hearts exhibited significantly enhanced PS associated with shortened TPS and TR90 compared with those from copper-adequate rat hearts. The +/-dL/dt and intracellular Ca**2+ transient decay rate were both enhanced in myocytes from copper-deficient rats. Nitric oxide synthase (NOS) activity was also greatly increased in these cells. These data indicate that impaired cardiac contractile function seen in copper-deficient whole hearts might not be due to depressed cardiac contractile function at the single cell level, but rather to other mechanisms such as cardiac fibrosis. The enhanced contractile function in cardiac myocytes may be an adaptive response to cardiac hypertrophy, as seen in hypertension.