Abstract 1438: Myofilament Calcium Sensitivity is Greater in Male than in Female Ventricular Myocytes
Hearts of males are significantly more prone to injury from ischemia-reperfusion induced Ca2+ overload than premenopausal female hearts. Our hypothesis is that sex-based differences in myocyte Ca2+ regulation and/or myofilament Ca2+ binding affinity predispose male cardiac myocytes to Ca-mediated dysfunction.
Methods: Myocytes were isolated from female (F) and male (M) Swiss Webster mice (9–12 weeks) using collagenase-based perfusion techniques. Sarcomere length (light diffraction) and Ca2+ (CaT) transients (fluo-3; F/Frest) were measured at pacing rates of 0.5– 4 Hz and at bath [Ca] of 0.5– 4mM.
Results: Under control conditions (1Hz; 1.5mM Ca2+) resting sarcomere length was not significantly different in M and F (average 1.80μ). Contraction magnitude (% sarcomere length) was significantly greater (p<.05) in M (10.2 ± 0.7%, n=34) vs F (7.3 ± 0.7%, n=30). However, CaT amplitude was greater (p<.05) in F (2.80± .22) vs M (2.28 ± .17). Contraction and CaT magnitudes decreased as pacing frequency increased (0.5 Hz to 4Hz), however, contraction magnitudes were always greater and CaT were always smaller in M vs F. Contractions and CaT both increased significantly with bath [Ca] in both M and F, but again contractions were always greater in M. An index of the myofilament Ca2+ binding affinity, the slope of the terminal portion of the CaT (F/Frest )) vs Sarcomere length (μ) plots (see figure⇓), was significantly greater (p<.05) in M (.92±.4, n=15) vs F(.12±.04, n=15).
Conclusion: Myofilament Ca2+ binding affinity a significantly greater in M versus F mouse myocytes, which should predisposes M myocytes to hypercontractile damage during periods of [Ca] overload.