Myofilament response to Ca2+ 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. 2007 Feb;292(2):R837-43. doi: 10.1152/ajpregu.00376.2006. Epub 2006 Oct 12.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Respiratory / physiopathology*
  • Actin Cytoskeleton / physiology*
  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Calcium / metabolism*
  • Calcium Signaling / physiology
  • Cell Separation
  • Estrogens / pharmacology
  • Female
  • Gonadal Steroid Hormones / pharmacology*
  • Guanidines / pharmacology
  • 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
  • Sodium-Calcium Exchanger / metabolism*
  • Sodium-Hydrogen Exchangers / metabolism*
  • Sulfones / pharmacology

Substances

  • Anti-Arrhythmia Agents
  • Estrogens
  • Gonadal Steroid Hormones
  • Guanidines
  • Sodium-Calcium Exchanger
  • Sodium-Hydrogen Exchangers
  • Sulfones
  • cariporide
  • Calcium