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

Components of excitation-contraction (E-C) coupling were compared in ventricular myocytes isolated from 3-mo-old male and female rats. Ca(2+) concentrations (fura-2) and cell shortening (edge detector) were measured simultaneously (37 degrees 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, Ca(2+) transients were smaller in females than in males and the rate of rise of the Ca(2+) transient was slower in females. Despite smaller contractions and Ca(2+) transients in females, Ca(2+) current density was similar in both groups. Sarcoplasmic reticulum Ca(2+) content, assessed with caffeine, did not differ between the sexes. However, E-C coupling gain (rate of Ca(2+) release/Ca(2+) 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 Ca(2+) release, spontaneous Ca(2+) sparks were evaluated (fluo-4, 37 degrees 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 DeltaF/F(0), 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 Ca(2+) 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 Ca(2+) release between the sexes.