Abstract 17008: Caveolin-3 Expression Optimizes Cardiac Conduction and Prolongs Endurance
Caveolin-3 (Cav-3) is a sarcolemmal scaffolding protein that has been identified in cellular pathways involved in cardiac remodeling and protection. Cardiac specific overexpression of Cav-3 has been shown to be protective against ischemic and hypertensive injury. However, caveolar effects on conduction have yet to be investigated. We hypothesized that Cav-3 plays an integral role in optimizing efficient cardiac conduction.
Methods: Transgenic mice with cardiac specific overexpression of Cav-3 (Cav-3 OE) and littermate controls (C) were subjected to telemetry implantation for 3 days in 12 hour light-dark cycles to obtain baseline data. Cav-3 OE and C were then injected with dobutamine, propranolol, and atropine individually and then monitored for heart rate response. Untrained Cav-3 OE and C were run on a mechanical treadmill to determine baseline cardiac endurance.
Results: Cav-3 OE and C mice displayed diurnal sleep patterns with maximal body core temperatures at midnight and minimal temperatures at noon. Cav-3 OE had significantly lower resting heart rates compared to control (464± 13 vs. 523± 14 bpm; n=4; P<0.001), however, while awake no significant differences were observed. Furthermore, Cav-3 OE mice had prolonged PR intervals (38.1± 1.0 vs. 34.5± 0.3 msec; n=4; P<0.05) and shortened QT compared to C (153± 3 vs. 171± 6 msec; n=4; P<0.05). Dobutamine caused rapid heart rate increase in both Cav-3 OE and C with no significant difference between maximal heart rate. However, Cav-3 OE mice recovered sooner from the stimulus and returned to basal heart rate nearly 50% faster than C. Atropine resulted in an immediate response in Cav-3 OE and then a secondary gradual maximum response at 60 minutes. Conversely, C gradually reached maximal response at 60 minutes and again had a longer recovery. Beta blockade with propranolol resulted in no significant differences. Interestingly, untrained Cav-3 OE mice were able to run twice as long as C (158± 299 vs. 70± 13 min; n=6; P<0.05).
Conclusion: Cav-3 OE mice revealed lower basal heart rates at rest with more dynamic response to adrenergic stimulus and inhibition of vagal tone, as well as prolonged endurance which are all suggestive of a trained heart-like phenotype.
- © 2013 by American Heart Association, Inc.