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

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 microM 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.