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Cardiac Alternans Do Not Rely on Diastolic Sarcoplasmic Reticulum Calcium Content Fluctuations
Open accessAbstract
Cardiac alternans are thought to be a precursor to life-threatening arrhythmias. Previous studies suggested that alterations in sarcoplasmic reticulum (SR) Ca 2+ content are either causative or not associated with myocyte Ca 2+ alternans. However, those studies used indirect measures of SR Ca 2+ . Here we used direct continuous measurement of intra-SR free [Ca 2+ ] ([Ca 2+ ] SR ) (using Fluo5N) during frequency-dependent Ca 2+ alternans in rabbit ventricular myocytes. We tested the hypothesis that alternating [Ca 2+ ] SR is required for Ca 2+ alternans. Amplitudes of [Ca 2+ ] SR depletions alternated in phase with cytosolic Ca 2+ transients and contractions. Some cells showed clear alternation in diastolic [Ca 2+ ] SR during alternans, with higher [Ca 2+ ] SR before the larger SR Ca 2+ releases. However, the extent of SR Ca 2+ release during the small beats was smaller than expected for the modest decrease in [Ca 2+ ] SR . In other cells, clear Ca 2+ alternans was observed without alternations in diastolic [Ca 2+ ] SR . Additionally, alternating cells were observed, in which diastolic [Ca 2+ ] SR fluctuations occurred interspersed by depletions in which the amplitude was unrelated to the preceding diastolic [Ca 2+ ] SR . In all forms of alternans, the SR Ca 2+ release rate was higher during large depletions than during small depletions. Although [Ca 2+ ] SR exerts major influence on SR Ca 2+ release, alternations in [Ca 2+ ] SR are not required for Ca 2+ alternans to occur. Rather, it seems likely that some other factor, such as ryanodine receptor availability after a prior beat (eg, recovery from inactivation), is of greater importance in initiating frequency-induced Ca 2+ alternans. However, once such a weak SR Ca 2+ release occurs, it can result in increased [Ca 2+ ] SR and further enhance SR Ca 2+ release at the next beat. In this way, diastolic [Ca 2+ ] SR alternans can enhance frequency-induced Ca 2+ alternans, even if they initiate by other means.
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Citations
Cited by
Calcium Cycling and Signaling in Cardiac Myocytes
Bers, D. M. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.113006.100455 · Cited by 1,302
Self-citationA Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates
Mahajan, A., Shiferaw, Y., Sato, D., Baher, A., Olcese, R., Xie, L.-H., Yang, M.-J., Chen, P.-S., Restrepo, J. G., Karma, A., et al. (2008) · Biophysical Journal · doi:10.1529/biophysj.106.98160 · Cited by 403
ter Keurs, H. E. D. J., & Boyden, P. A. (2007) · Physiological Reviews · doi:10.1152/physrev.00011.2006 · Cited by 356
Cardiac Sarcoplasmic Reticulum Calcium Leak: Basis and Roles in Cardiac Dysfunction
Bers, D. M. (2014) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153308 · Cited by 329
Self-citationPark, D.-R., Nam, T.-S., Kim, Y.-W., Lee, S.-H., & Kim, U.-H. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000489441 · Cited by 19
Metadata
- Authors
- Picht, E., DeSantiago, J., Blatter, L. A., & Bers, D. M.
- Venue
- Circulation Research
- Published
- 2006-09-29
- Volume
- 99
- Issue
- 7
- Pages
- 740-748
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2101742222
- Cited by
- 170
- References
- 0
- FWCI
- 7.44
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Picht, E., DeSantiago, J., Blatter, L. A., & Bers, D. M. (2006). Cardiac Alternans Do Not Rely on Diastolic Sarcoplasmic Reticulum Calcium Content Fluctuations. Circulation Research. https://doi.org/10.1161/01.res.0000244002.88813.91
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