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Am J Physiol Heart Circ Physiol (August 28, 2003). doi:10.1152/ajpheart.00557.2003
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Submitted on June 15, 2003
Accepted on August 20, 2003

Gender Differences in Sarcoplasmic Reticulum Calcium Loading After Isoproterenol

Jarvis Chen1, John Petranka1, Ken Yamamura1, Robert E. London1, Charles Steenbergen2, and Elizabeth Murphy1*

1 Department of Labories of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, RTP, NC, USA
2 Department of Pathology, Duke University Medical Center, Durham, NC, USA

* To whom correspondence should be addressed. E-mail: murphy1{at}niehs.nih.gov.

We have reported that males exhibit enhanced myocardial ischemia-reperfusion injury compared to females under hypercontractile conditions associated with increased sarcoplasmic reticulum (SR) calcium (Ca2+). We therefore examined whether there were gender differences in SR Ca2+. We used the NMR Ca2+ indicator TFBAPTA to measure SR Ca2+ in perfused rabbit hearts. Addition of isoproterenol increased SR Ca2+ in males from a baseline value of 1.13±0.07 mM to 1.52±0.24 mM (p<0.05). Female hearts had a basal SR Ca2+ that was not significantly different than males (1.04±0.03 mM), and addition of isoproterenol to females resulted in a time-average SR Ca2+ (0.97±0.07 mM) that was significantly less than in males. To confirm this gender difference in SR Ca2+ after isoproterenol, we measured caffeine-induced release of SR Ca2+ with fura-2 in isolated ventricular myocytes. Ca2+ release after caffeine addition in untreated male myocytes was 377±41 nM and increased to 650±55 nM in isoproterenol treated myocytes (p<0.05). Ca2+ release after caffeine addition in untreated females was 376±27 nM and increased to 503±49 nM with isoproterenol treatment, significantly less than in male myocytes treated with isoproterenol (p<0.05). Treatment of female myocytes with L-NAME, an inhibitor of nitric oxide synthase (NOS) resulted in an SR Ca2+ release that was higher than that measured in females treated only with isoproterenol and not significantly different than the SR Ca2+ release measured in males with isoproterenol. We also report that female myocytes have significantly higher levels of nNOS. This gender difference in SR Ca2+ handling may contribute to reduced ischemia-reperfusion injury observed in females.




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