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Am J Physiol Regul Integr Comp Physiol 292: R837-R843, 2007. First published October 12, 2006; doi:10.1152/ajpregu.00376.2006
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Sex Differences in Renal and Cardiovascular Function: Physiology and Pathophysiology

Myofilament response to Ca2+ and Na+/H+ exchanger activity in sex hormone-related protection of cardiac myocytes from deactivation in hypercapnic acidosis

Tepmanas Bupha-Intr,2 Jonggonnee Wattanapermpool,2 James R. Peña,1 Beata M. Wolska,1 and R. J. Solaro1

1Department of Physiology and Biophysics, Medicine and Center for Cardiovascular Research, College of Medicine, University of Illinois at Chicago, Chicago, Illinois; and 2Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand

Submitted 31 May 2006 ; accepted in final form 3 October 2006

Compared to sham-operated controls, myofilaments from hearts of ovariectomized (OVX) rats demonstrate an increase in Ca2+ sensitivity with no change in maximum tension (Wattanapermpool J and Reiser PJ. Am J Physiol 277: H467–H473, 1999). To test the significance of this modification in intact cells, we compared intracellular Ca2+ transients and shortening of ventricular myocytes isolated from sham and 10-wk OVX rats. There was a decrease in the peak Ca2+ transient with prolonged 50% decay time in OVX cardiac myocytes without changes in the resting intracellular Ca2+ concentration. Percent cell shortening was also depressed, and relaxation was prolonged in cardiac myocytes from OVX rats compared with shams. Ovariectomy induced a sensitization of the myofilaments to Ca2+. Hypercapnic acidosis suppressed the shortening of OVX myocytes to a lesser extent than that detected in shams. Moreover, a larger compensatory increase in %cell shortening was obtained in OVX myocytes during prolonged acidosis. The elevated compensation in cell shortening was related to a higher amount of increase in the amplitude of the Ca2+ transient in OVX myocytes. However, these differences in Ca2+ transients and %cell shortening were no longer evident in the presence of 1 µM cariporide, a specific inhibitor of Na+/H+ exchanger type 1 (NHE1). Our results indicate that deprivation of female sex hormones modulates the intracellular Ca2+ concentration in cardiac myocytes, possibly via an increased NHE1 activity, which may act in concert with Ca2+ hypersensitivity of myofilament activation as a determinant of sex differences in cardiac function.

heart; estrogen; sarcomeric proteins; sodium; proton exchanger



Address for reprint requests and other correspondence: R. J. Solaro, Dept. of Physiology and Biophysics, College of Medicine, Univ. of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612–7342 (e-mail: solarorj{at}uic.edu)




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