Related Experiment Videos
Age and gender differences in excitation-contraction coupling of the rat ventricle
N Leblanc1, D Chartier, H Gosselin
1Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada H1T 1C8 leblancn@alize.ere.umontreal.ca
Insights
Post-pubertal female rats show reduced papillary muscle contractility and altered calcium handling compared to males. These gender-specific differences in excitation-contraction coupling are linked to sarcoplasmic reticulum calcium storage and release mechanisms.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Molecular Cardiology
Background:
- Cardiac function exhibits age and gender-specific variations.
- Understanding these differences is crucial for diagnosing and treating heart conditions.
Purpose of the Study:
- To investigate post-pubertal gender-specific differences in rat papillary muscle contractility.
- To explore electrophysiological properties and calcium transients in ventricular myocytes.
- To identify the cellular basis for observed gender-related changes in cardiac function.
Main Methods:
- Isometric and isotonic contractility measurements of rat papillary muscles.
- Whole-cell patch clamp technique for recording action potentials and ionic currents in isolated myocytes.
- Indo-1 fluorescence measurements to assess intracellular calcium transients.
Main Results:
- Female rats (≥6 months) exhibited reduced papillary muscle contractility and slower contraction/relaxation dynamics compared to age-matched males.
- No significant gender or age-related differences were found in action potentials or major potassium currents (IK1, Ito, IK).
- While L-type calcium current (ICa(L)) was similar, calcium transients in older female myocytes showed reduced amplitude and impaired relaxation, indicating altered calcium handling.
Conclusions:
- Post-pubertal development leads to significant gender-specific alterations in cardiac excitation-contraction coupling in rats.
- These changes are likely attributable to differences in sarcoplasmic reticulum calcium handling, not fundamental electrophysiological properties.
- The findings highlight the importance of considering gender in cardiovascular research and clinical practice.
Abstract:
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 C). Action potentials from male and female myocytes of 3- and 9-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 (IK1), transient outward (Ito) and sustained (IK) K+ currents displayed little, if any dependence on age or gender. 4. L-type Ca2+ current (ICa(L)) measured in caesium-loaded myocytes (35 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.