CALL FOR PAPERS Sex Differences in Renal and Cardiovascular Function: Physiology and Pathophysiology Myofilament response to Ca and Na /H exchanger activity in sex hormone-related protection of cardiac myocytes from deactivation in hypercapnic acidosis

Bupha-Intr T, Wattanapermpool J, Peña JR, Wolska BM, Solaro RJ. Myofilament response to Ca and Na /H exchanger activity in sex hormone-related protection of cardiac myocytes from deactivation in hypercapnic acidosis. Am J Physiol Regul Integr Comp Physiol 292: R837–R843, 2007. First published October 12, 2006; doi:10.1152/ajpregu.00376.2006.—Compared to sham-operated controls, myofilaments from hearts of ovariectomized (OVX) rats demonstrate an increase in Ca 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 Ca transients and shortening of ventricular myocytes isolated from sham and 10-wk OVX rats. There was a decrease in the peak Ca transient with prolonged 50% decay time in OVX cardiac myocytes without changes in the resting intracellular Ca 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 Ca . 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 Ca transient in OVX myocytes. However, these differences in Ca transients and %cell shortening were no longer evident in the presence of 1 M cariporide, a specific inhibitor of Na /H exchanger type 1 (NHE1). Our results indicate that deprivation of female sex hormones modulates the intracellular Ca concentration in cardiac myocytes, possibly via an increased NHE1 activity, which may act in concert with Ca hypersensitivity of myofilament activation as a determinant of sex differences in cardiac function.