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Updated: May 18, 2026
Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Irregular rhythm adversely influences calcium handling in ventricular myocardium: implications for the interaction
Liang-han Ling1, Ouda Khammy, Melissa Byrne
1Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Insights
Irregular heart rhythms in heart failure (HF) impair calcium handling in cardiomyocytes, worsening HF progression. Controlling heart rhythm may benefit HF patients by improving excitation-contraction coupling.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Atrial fibrillation combined with heart failure (HF) accelerates HF progression despite adequate rate control.
- The underlying mechanism may involve altered ventricular cardiomyocyte excitation-contraction coupling due to irregular rhythms.
Purpose of the Study:
- To investigate if irregular ventricular rhythm alters cardiomyocyte excitation-contraction coupling, contributing to HF progression.
- To test the hypothesis that rhythm irregularity impacts calcium handling in heart failure.
Main Methods:
- Rat ventricular myocytes were electrically stimulated with irregular versus regular patterns.
- Intracellular calcium transients were measured using Fura-2AM fluorescence spectroscopy.
- Calcium-handling protein expression was analyzed in rat myocytes and human HF patient left ventricular samples.
Main Results:
- Irregular pacing in rat myocytes reduced sarcoplasmic reticulum calcium (Ca2+) ATPase expression and phospholamban phosphorylation.
- Peak Ca2+ transients were significantly reduced in irregularly paced myocytes.
- HF patients with atrial fibrillation showed decreased Ca2+ ATPase expression and phospholamban phosphorylation compared to those in sinus rhythm.
Conclusions:
- Ventricular rhythmicity significantly impacts excitation-contraction coupling by altering calcium-handling proteins.
- These findings suggest that controlling heart rhythm could be therapeutically beneficial for heart failure patients.
Background:
Despite adequate rate control, the combination of atrial fibrillation with heart failure (HF) has been shown, in a number of studies, to hasten HF progression. In this context, we aimed to test the hypothesis that an irregular ventricular rhythm causes an alteration in ventricular cardiomyocyte excitation-contraction coupling which contributes to the progression of HF.
Methods And Results:
We investigated the effects of electrical field stimulation (average frequency 2 Hz) in an irregular versus regular drive train pattern on the expression of calcium-handling genes and proteins in rat ventricular myocytes. The effect of rhythm on intracellular calcium transients was examined using Fura-2AM fluorescence spectroscopy. In conjunction, calcium-handling protein expression was examined in left ventricular samples obtained from end-stage HF patients, in patients with either persistent atrial fibrillation or sinus rhythm. Compared with regularly paced ventricular cardiomyocytes, in cells paced irregularly for 24 hours, there was a significant reduction in the expression of sarcoplasmic reticulum calcium (Ca(2+)) ATPase together with reduced serine-16 phosphorylation of phospholamban. These findings were accompanied by a 59% reduction (P<0.01) in the peak Ca2+ transient in irregulary paced myocytes compared with those with regular pacing. Consistent with these observations, we observed a 54% (P<0.05) decrease in sarcoplasmic reticulum Ca(2+)ATPase protein expression and an 85% (P<0.01) reduction in the extent of phosphorylation of phospholamban in the left ventricular myocardium of HF patients in atrial fibrillation compared with those in sinus rhythm.
Conclusions:
Together, these data demonstrate that ventricular rhythmicity contributes significantly to excitation-contraction coupling by altering the expression and activity of key calcium-handling proteins. These data suggest that control of rhythm may be of benefit in patients with HF.
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