Sex differences in intracellular Ca2+ accumulation following eccentric contractions of rat skeletal muscle in vivo

Abstract

It is commonly believed that estrogen and sex influences play significant effects in skeletal muscle damage following eccentric exercise. The mechanistic bases for this sex-specific phenomenon remain to be resolved. The muscle damage has been linked to loss of Ca(2+) homeostasis and resultant intramyocyte Ca(2+) ([Ca(2+)](i)) accumulation; therefore, we tested the hypothesis that the greater eccentric exercise-induced muscle damage in males would be associated with more pronounced [Ca(2+)](i) accumulation. The intact spinotrapezius muscle of adult Wistar rats [male, female, and ovariectomized (OVX)-to investigate the effects of estrogen] was exteriorized. Tetanic eccentric contractions (100 Hz, 700-ms duration, 20 contractions/min for a total of 10 sets of 50 contractions) were elicited by electrical stimulation during synchronized muscle stretch of 10% resting muscle length. The fluorescence ratio (F(340)/F(380) nm) was determined from images captured following each set of contractions, and fura-2 AM was used to estimate [Ca(2+)](i) and changes thereof. Following eccentric contractions, [Ca(2+)](i) increased significantly in male (42.8 ± 5.3%, P < 0.01) but not in female (9.4 ± 3.5%) rats. OVX evidenced an intermediate response (17.0 ± 1.2%) that remained significantly reduced compared with males. These results demonstrate that females maintain [Ca(2+)](i) homeostasis following novel eccentric contractions, whereas males do not, which is consistent with a role for elevated [Ca(2+)](i) in eccentric exercise-induced muscle damage. The presence of normal estrogen levels is not obligatory for the difference between the sexes.