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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2007-02, Vol.292 (2), p.R837-R843
• Main Authors: Bupha-Intr, Tepmanas, Wattanapermpool, Jonggonnee, Pena, James R, Wolska, Beata M, Solaro, R. J
• Format: Article
• Language: English
• Subjects: Acidosis, Respiratory - physiopathology; Actin Cytoskeleton - physiology; Animals; Anti-Arrhythmia Agents - pharmacology; Calcium; Calcium - metabolism; Calcium Signaling - physiology; Cell Separation; Cells; Estrogens - pharmacology; Female; Gonadal Steroid Hormones - pharmacology; Guanidines - pharmacology; Heart; Hormones; Hydrogen-Ion Concentration; Hypercapnia - physiopathology; In Vitro Techniques; Kinetics; Muscle Fibers, Skeletal - physiology; Myocardial Contraction - physiology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Ovariectomy; Rats; Rats, Sprague-Dawley; Rodents; Sodium-Calcium Exchanger - metabolism; Sodium-Hydrogen Exchangers - metabolism; Sulfones - pharmacology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00376.2006

1 Department of Physiology and Biophysics, Medicine and Center for Cardiovascular Research, College of Medicine, University of Illinois at Chicago, Chicago, Illinois; and 2 Department 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 Ca 2+ 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 2+ transients and shortening of ventricular myocytes isolated from sham and 10-wk OVX rats. There was a decrease in the peak Ca 2+ transient with prolonged 50% decay time in OVX cardiac myocytes without changes in the resting intracellular Ca 2+ 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 2+ . 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 2+ transient in OVX myocytes. However, these differences in Ca 2+ transients and %cell shortening were no longer evident in the presence of 1 µM cariporide, a specific inhibitor of Na + /H + exchanger type 1 (NHE 1 ). Our results indicate that deprivation of female sex hormones modulates the intracellular Ca 2+ concentration in cardiac myocytes, possibly via an increased NHE 1 activity, which may act in concert with Ca 2+ 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 )