Sex differences in the response of rat heart ventricle to calcium

Calcium (Ca2+) is a key mediator of myocardial function. Calcium regulates contraction, and disruption of myocellular Ca2+ handling plays a role in cardiac pathologies such as arrhythmias and heart failure. This investigation examines sex differences in sensitivity of the contractile proteins to Ca2+ and myofibrillar Ca2+ delivery in the ventricular myocardium. Sensitivity of contractile proteins to Ca2+ was measured in weight-matched male and female Sprague-Dawley rats using the skinned ventricular papillary muscle fiber and Ca(2+)-stimulated Mg(2+)-dependent adenosine triphosphatase (ATPase) activity methodologies. Calcium delivery was examined by measuring the contractile response to a range of extracellular Ca2+ concentrations in isolated ventricular myocytes, papillary muscle, and the isolated perfused whole heart. Findings from studies in the whole heart suggest that at a fixed preload, the male left ventricle generates more pressure than a female ventricle over a range of extracellular Ca2+ concentrations. In contrast, results from myocyte and papillary muscle studies suggest that females require less extracellular Ca2+ to elicit a similar contractile response. Results obtained from the 2 methods used to determine sex differences in Ca2+ sensitivity were equivocal. Further studies are required to elucidate sex differences in myocardial Ca2+ handling and the reasons for disparate results in different heart muscle preparations. The results of these studies will lead to the design of sex-optimized therapeutic interventions for cardiac disease.