Age and gender differences in excitation-contraction coupling of the rat ventricle

1. The objective of this study was to determine potential post-pubertal gender-specific differences in the contractility of papillary muscles, the electrophysiological properties and Ca2+ transients of freshly dissociated ventricular myocytes from the rat heart. 2. The contractions of rat papillary muscles from 2- to 14-month-old male and female rats were studied under isometric and isotonic conditions (29 degrees C). While the hearts of young (2-4 months) male and female rats displayed a similar contractile profile, papillary muscles of female rats aged 6 months and older exhibited smaller isometric and isotonic contractions, smaller maximal rates of tension and shortening development and decline (+/- DT/dt and +/- DL/dt) velocities during both the onset and relaxation phases, and shorter contractions than age-matched males. 3. To explore the possible cellular basis accounting for these differences,, action potentials and macroscopic currents were recorded from freshly dissociated myocytes using the whole-cell patch clamp technique (35 degrees C). Action potentials from male and female myocytes of 3- and B-month-old rats did not vary as a function of age or gender. Consistent with these results, the magnitude (expressed in pA pF(-1)), voltage-dependence and kinetics of the inward rectifier (I-K1), transient outward (I-to) and sustained (I-K) K+ currents displayed little, if any dependence on age or gender. 4. L-type Ca2+ current (I-Ca(L)) measured in caesium-loaded myocytes (35 degrees C) from male and female rats of 3, 6 and 9 months of age exhibited similar characteristics. In contrast, while Ca2+ transients measured with indo-1 were similar between 3-month-old male and female rat myocytes, Ca2+ transients of 10-month-old female myocytes were significantly reduced and showed a diminished rate of relaxation in comparison with those recorded in male rats of similar age. 5. These results suggest that important gender-related changes in excitation-contraction coupling occur following puberty, probably due to differences in Ca2+ handling capabilities at the level of the sarcoplasmic reticulum.