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1 Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, United States; Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States
2 Physiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
3 Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States
4 Biology, Ursinus College, Collegeville, Pennsylvania, United States
5 Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, United States
6 Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: Kenneth.Margulies{at}uphs.upenn.edu.
Recent studies have identified sex differences in heart function that may affect the risk of developing heart failure. We hypothesized that there are fundamental differences in calcium (Ca) regulation in cardiac myocytes of males and premenopausal females. METHODS: Isometric force transients (n=45) were measured at various frequencies (FFR) (0.5,1.0,1.5,2.0 Hz) during either changes in bath Ca ([Ca]o) (1.0,1.75,3.5,7.0 mM) or length (LT) (20,40,60,80,100% Lmax) in RV trabeculae from normal male (MT) and premenopausal female (FT) cats. Force-Ca measurements were also obtained in chemically skinned trabeculae. RESULTS: Under basal conditions (0.5 Hz, 1.75 mM Ca, 80% Lmax) both MT and FT achieved similar developed forces (DF) (MT 11±1, FT=10±1 mN/mm2). At low rates and lengths there is no sex difference. At higher preloads and rates, there is a separation in DF in MT and FT. At basal [Ca]o both MT and FT exhibited positive FFR (2.0 Hz, 1.75 mM Ca: MT 38±3, FT 21±4 mN/mm2); however, at higher [Ca]o, MT achieved greater DF (2.0 Hz, 7.0 mM Ca: MT 40±3 and FT=24±4 mN/mm2). We detected no sex difference in myofilament Ca sensitivity at a sarcomere length of 2.1 µm. However, rapid cooling contractures indicated greater SR Ca load in MT at higher frequencies. CONCLUSION: Despite virtually identical contractile performance under basal conditions, significant sex differences emerge under conditions of increased physiological stress. Given the lack of sex differences in myofilament Ca sensitivity, these studies suggest fundamental sex differences in cellular Ca regulation to achieve contractile reserve, with myocardium from males exhibiting higher SR Ca load.
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