Sex differences in mechanisms of cardiac excitation-contraction coupling in rat ventricular myocytes

Abstract

Components of excitation-contraction (E-C) coupling were compared in ventricular myocytes isolated from 3-mo-old male and female rats. Ca2+ concentrations (fura-2) and cell shortening (edge detector) were measured simultaneously (37°C). Membrane potential and ionic currents were measured with microelectrodes. Action potentials were similar in male and female myocytes, but contractions were smaller and slower in females. In voltage-clamped cells, peak contractions were smaller in females than in males (5.1 ± 0.7% vs. 7.7 ± 0.8% diastolic length, P < 0.05). Similarly, Ca2+ transients were smaller in females than in males and the rate of rise of the Ca2+ transient was slower in females. Despite smaller contractions and Ca2+ transients in females, Ca2+ current density was similar in both groups. Sarcoplasmic reticulum Ca2+ content, assessed with caffeine, did not differ between the sexes. However, E-C coupling gain (rate of Ca2+ release/Ca2+ current) was smaller in females than in males (157.0 ± 15.6 vs. 338.4 ± 54.3 (nM/s)/(pA/pF), P < 0.05). To determine whether the reduced gain in female cells was due to changes in unitary Ca2+ release, spontaneous Ca2+ sparks were evaluated (fluo-4, 37°C). Spark frequencies and widths were similar in both groups, but spark amplitudes were smaller in females than in males (0.56 ± 0.01 vs. 0.64 ± 0.01 ΔF/F0, P < 0.05). Spark durations also were shorter in females than in males (full duration at half-maximum = 14.86 ± 0.17 vs. 16.25 ± 0.27 ms, P < 0.05). These observations suggest that decreases in the size and duration of Ca2+ sparks contributes to the decrease in E-C coupling gain in female myocytes. Thus, differences in cardiac contractile function arise, in part, from differences in unitary Ca2+ release between the sexes.