Increase in calcium responsiveness of cardiac myofilament activation in ovariectomized rats

Abstract

To evaluate a possible role of ovarian sex hormones in the Ca2+responsiveness of cardiac myofilament activation, the relations of pCa (-log Ca2+molar concentration) to actomyosin adenosine triphosphatase (ATPase) activity of isolated myofibrillar preparations from 8-10 week ovariectomized (Ovx) rat hearts were compared with those from sham-operated hearts. Deficiency of ovarian sex hormones in plasma of ovariectomized rats was indirectly verified by a significant reduction in uterine weights. Body weights of the ovariectomized rats were significantly greater than those of sham-operated controls. Despite a significant increase in heart weight of 10 week ovariectomized animals, the percent of heart weight-to-body weight ratio was not different from control group. The maximum myofibrillar ATPase activity at pH 7.0 was significantly suppressed after ovariectomy in both eight and ten week groups. However, the maximum ATPase activity at pH 6.5 was significantly suppressed only in 10 week ovariectomized hearts. Surprisingly, in every condition with depressed maximum myofibrillar ATPase activity, the pCa-actomyosin ATPase relationships of ovariectomized cardiac myofilaments demonstrated a significant leftward shift in pCa50(-log half-maximally Ca2+activation) from those of sham-operated controls. There was, however, no change in the Hill-coefficient of these cardiac myofilaments after ovariectomy. Analysis of myofilament proteins using gel electrophoresis demonstrated neither change nor loss of any thin filament proteins. These results indicate a possible modulating effect of ovarian sex hormone deficiency on the Ca2+responsiveness of cardiac myofilament activation by induction of myofilament Ca2+hypersensitivity but suppression of maximum myofibrillar ATPase activity.