Atrial Myocyte Function and Ca2+ Handling Is Associated with Inborn Aerobic Capacity

Anne Berit Johnsen,Godfrey L Smith,Marcia Alves,Tomas Stølen,Lauren G Koch,Ulrik Wisløff,Geir Slupphaug,Steven L Britton,Morten A Høydal,Mirta M L Sousa,Natale P L Rolim,Xun Ai

doi:10.1371/journal.pone.0076568

Abstract

BackgroundAlthough high aerobic capacity is associated with effective cardiac function, the effect of aerobic capacity on atrial function, especially in terms of cellular mechanisms, is not known. We aimed to investigate whether rats with low inborn maximal oxygen uptake (VO2 max) had impaired atrial myocyte contractile function when compared to rats with high inborn VO2 max.Methods and ResultsAtrial myocyte function was depressed in Low Capacity Runners (LCR) relative to High Capacity Runners (HCR) which was associated with impaired Ca2+ handling. Fractional shortening was 52% lower at 2 Hz and 60% lower at 5 Hz stimulation while time to 50% relengthening was 43% prolonged and 55% prolonged, respectively. Differences in Ca2+ amplitude and diastolic Ca2+ level were observed at 5 Hz stimulation where Ca2+ amplitude was 70% lower and diastolic Ca2+ level was 11% higher in LCR rats. Prolonged time to 50% Ca2+ decay was associated with reduced sarcoplasmic reticulum (SR) Ca2+ ATPase function in LCR (39%). Na+/Ca2+ exchanger activity was comparable between the groups. Diastolic SR Ca2+ leak was increased by 109%. This could be partly explained by increased ryanodine receptors phosphorylation at the Ca2+-calmodulin-dependent protein kinase-II specific Ser-2814 site in LCR rats. T-tubules were present in 68% of HCR cells whereas only 33% LCR cells had these structures. In HCR, the significantly higher numbers of cells with T-tubules were combined with greater numbers of myocytes where Ca2+ release in the cell occurred simultaneously in central and peripheral regions, giving rise to faster and more spatial homogenous Ca2+-signal onset.ConclusionThis data demonstrates that contrasting for low or high aerobic capacity leads to diverse functional and structural remodelling of atrial myocytes, with impaired contractile function in LCR compared to HCR rats.

Highlights

Despite the important contribution of atria to refilling of the ventricles during increased workload such as physical activity, there are limited data on the association between atrial function and aerobic capacity, especially in terms of cellular mechanisms
Ca2+-handling We found that atrial myocyte Ca2+- handling was significantly impaired in Low Capacity Runners (LCR) rats compared to High Capacity Runners (HCR) rats
Compared to rats with high aerobic capacity we found that low aerobic capacity in LCR rats was associated with reduced atrial myocyte contractility and diastolic relaxation that were associated with impaired Ca2+-handling

Summary

Introduction

Despite the important contribution of atria to refilling of the ventricles during increased workload such as physical activity, there are limited data on the association between atrial function and aerobic capacity, especially in terms of cellular mechanisms. Recent studies have shown that failure to increase atrial function on exercise impairs compensatory late diastolic filling with increased heart rate. This contributes to genesis of exertional dyspnoea [1,2]. It is well established that aerobic exercise training improves left ventricular cardiac function with increased cardiac output during systole and faster relaxation during diastole [3] These functional alterations of the heart are supported by several studies which indicate a clear association between both training induced and high inborn aerobic capacity with improved left ventricular myocyte function and Ca2+ handling (reviewed in Kemi et al [4]). We aimed to investigate whether rats with low inborn maximal oxygen uptake (VO2 max) had impaired atrial myocyte contractile function when compared to rats with high inborn VO2 max

Objectives

Methods

Results

Discussion

Conclusion