| Title: | "Cardiac contraction, calcium transients, and myofilament calcium sensitivity fluctuate with the estrous cycle in young adult female mice" |
| Author(s): | MacDonald JK; Pyle WG; Reitz CJ; Howlett SE; |
| Address: | "Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada;" |
| Journal Title: | Am J Physiol Heart Circ Physiol |
| DOI: | 10.1152/ajpheart.00730.2013 |
| ISSN/ISBN: | 1522-1539 (Electronic) 0363-6135 (Linking) |
| Abstract: | "This study established conditions to induce regular estrous cycles in female C57BL/6J mice and investigated the impact of the estrous cycle on contractions, Ca2+ transients, and underlying cardiac excitation-contraction (EC)-coupling mechanisms. Daily vaginal smears from group-housed virgin female mice were stained to distinguish estrous stage (proestrus, estrus, metestrus, diestrus). Ventricular myocytes were isolated from anesthetized mice. Contractions and Ca2+ transients were measured simultaneously (4 Hz, 37 degrees C). Interestingly, mice did not exhibit regular cycles unless they were exposed to male pheromones in bedding added to their cages. Field-stimulated myocytes from mice in estrus had larger contractions ( approximately 2-fold increase), larger Ca2+ transients ( approximately 1.11-fold increase), and longer action potentials (>2-fold increase) compared with other stages. Larger contractions and Ca2+ transients were not observed in estrus myocytes voltage-clamped with shorter action potentials. Voltage-clamp experiments also demonstrated that estrous stage had no effect on Ca2+ current, EC-coupling gain, diastolic Ca2+, sarcoplasmic reticulum (SR) Ca2+ content, or fractional release. Although contractions were largest in estrus, myofilament Ca2+ sensitivity was lowest (EC50 values approximately 1.15-fold higher) in conjunction with increased phosphorylation of myosin binding protein C in estrus. Contractions were enhanced in ventricular myocytes from mice in estrus because action potential prolongation increased SR Ca2+ release. These findings demonstrate that cyclical changes in reproductive hormones associated with the estrous cycle can influence myocardial electrical and contractile function and modify Ca2+ homeostasis. However, such changes are unlikely to occur in female mice housed in groups under conventional conditions, since these mice do not exhibit regular estrous cycles" |
| Keywords: | "Action Potentials Animals *Calcium Signaling Carrier Proteins/metabolism Electric Stimulation Estrous Cycle/*metabolism Excitation Contraction Coupling Female Mice Mice, Inbred C57BL *Myocardial Contraction Myocardium/*metabolism Myofibrils/*metabolism Ph;" |
| Notes: | "MedlineMacDonald, Jennifer K Pyle, W Glen Reitz, Cristine J Howlett, Susan E eng MOP 97973/Canadian Institutes of Health Research/Canada Research Support, Non-U.S. Gov't 2014/01/28 Am J Physiol Heart Circ Physiol. 2014 Apr 1; 306(7):H938-53. doi: 10.1152/ajpheart.00730.2013. Epub 2014 Jan 24" |
