Calcium (Ca 2+ ) is a key mediator of myocardial function. Calcium regulates contraction, and disruption of myocellular Ca 2+ 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 Ca 2+ and myofibrillar Ca 2+ delivery in the ventricular myocardium. Sensitivity of contractile proteins to Ca 2+ was measured in weight-matched male and female SpragueDawley 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 Ca 2+ 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 Ca 2+ concentrations. In contrast, results from myocyte and papillary muscle studies suggest that females require less extracellular Ca 2+ to elicit a similar contractile response. Results obtained from the 2 methods used to determine sex differences in Ca 2+ sensitivity were equivocal. Further studies are required to elucidate sex differences in myocardial Ca 2+ 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.Calcium (Ca 2+ ) is a key mediator of myocardial cell function. Calcium initiates contraction and regulates contractile force on a beat-to-beat basis. Calcium also acts as a 2nd messenger for signal transduction pathways that modulate metabolism, hypertrophic cell growth, and apoptosis (del Monte and Hajjar 2002;Lynch and Michalak 2002). In the heart, the strength of contractile force is regulated in 2 ways. The 1st way is by altering the amount of Ca 2+ delivered to the contractile proteins. That is, an increase or decrease in the delivery of Ca 2+ to the contractile proteins results in a greater or reduced contractile force, respectively. The 2nd way is by altering the sensitivity of the myofibrils (contractile proteins) to Ca 2+ . Therefore, in the presence of the same concentration of intracellular Ca 2+ , an increase or decrease in the sensitivity of the myofibrils to Ca 2+ results in an increase or decrease in contractile force, respectively. Myofibrillar Ca 2+ sensitivity has been shown to be altered by the phosphorylation state of regulatory proteins (
DNA replication in Escherichia coli is initiated by DnaA binding to oriC, the replication origin. During the process of assembly of the replication factory, the DnaA is released back into the cytoplasm, where it is competent to reinitiate replication. Premature reinitiation is prevented by binding SeqA to newly formed GATC sites near the replication origin. Resolution of the resulting SeqA cluster is one aspect of timing for reinitiation. A Markov model accounting for the competition between SeqA binding and methylation for one or several GATC sites relates the timing to reaction rates, and consequently to the concentrations of SeqA and methylase. A model is proposed for segregation, the motion of the two daughter DNAs into opposite poles of the cell before septation. This model assumes that the binding of SeqA and its subsequent clustering results in loops from both daughter nucleoids attached to the SeqA cluster at the GATC sites. As desequestration occurs, the cluster is divided in two, one associated with each daughter. As the loops of DNA uncoil, the two subclusters migrate apart due to the Brownian ratchet effect of the DNA loop.
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