Cardiac alternans do not rely on diastolic sarcoplasmic reticulum calcium content fluctuations

Eckard Picht, Jaime DeSantiago, Lothar A. Blatter, Donald M Bers

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Cardiac alternans are thought to be a precursor to life-threatening arrhythmias. Previous studies suggested that alterations in sarcoplasmic reticulum (SR) Ca content are either causative or not associated with myocyte Ca alternans. However, those studies used indirect measures of SR Ca. Here we used direct continuous measurement of intra-SR free [Ca] ([Ca]SR) (using Fluo5N) during frequency-dependent Ca alternans in rabbit ventricular myocytes. We tested the hypothesis that alternating [Ca]SR is required for Ca alternans. Amplitudes of [Ca]SR depletions alternated in phase with cytosolic Ca transients and contractions. Some cells showed clear alternation in diastolic [Ca]SR during alternans, with higher [Ca]SR before the larger SR Ca releases. However, the extent of SR Ca release during the small beats was smaller than expected for the modest decrease in [Ca]SR. In other cells, clear Ca alternans was observed without alternations in diastolic [Ca]SR. Additionally, alternating cells were observed, in which diastolic [Ca]SR fluctuations occurred interspersed by depletions in which the amplitude was unrelated to the preceding diastolic [Ca]SR. In all forms of alternans, the SR Ca release rate was higher during large depletions than during small depletions. Although [Ca]SR exerts major influence on SR Ca release, alternations in [Ca]SR are not required for Ca 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 alternans. However, once such a weak SR Ca release occurs, it can result in increased [Ca]SR and further enhance SR Ca release at the next beat. In this way, diastolic [Ca]SR alternans can enhance frequency-induced Ca alternans, even if they initiate by other means.

Original languageEnglish (US)
Pages (from-to)740-748
Number of pages9
JournalCirculation Research
Volume99
Issue number7
DOIs
StatePublished - Oct 2006
Externally publishedYes

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Sarcoplasmic Reticulum
Calcium
Muscle Cells
Ryanodine Receptor Calcium Release Channel

Keywords

  • Alternans
  • Calcium
  • Excitation/contraction coupling
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cardiac alternans do not rely on diastolic sarcoplasmic reticulum calcium content fluctuations. / Picht, Eckard; DeSantiago, Jaime; Blatter, Lothar A.; Bers, Donald M.

In: Circulation Research, Vol. 99, No. 7, 10.2006, p. 740-748.

Research output: Contribution to journalArticle

Picht, Eckard ; DeSantiago, Jaime ; Blatter, Lothar A. ; Bers, Donald M. / Cardiac alternans do not rely on diastolic sarcoplasmic reticulum calcium content fluctuations. In: Circulation Research. 2006 ; Vol. 99, No. 7. pp. 740-748.
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abstract = "Cardiac alternans are thought to be a precursor to life-threatening arrhythmias. Previous studies suggested that alterations in sarcoplasmic reticulum (SR) Ca content are either causative or not associated with myocyte Ca alternans. However, those studies used indirect measures of SR Ca. Here we used direct continuous measurement of intra-SR free [Ca] ([Ca]SR) (using Fluo5N) during frequency-dependent Ca alternans in rabbit ventricular myocytes. We tested the hypothesis that alternating [Ca]SR is required for Ca alternans. Amplitudes of [Ca]SR depletions alternated in phase with cytosolic Ca transients and contractions. Some cells showed clear alternation in diastolic [Ca]SR during alternans, with higher [Ca]SR before the larger SR Ca releases. However, the extent of SR Ca release during the small beats was smaller than expected for the modest decrease in [Ca]SR. In other cells, clear Ca alternans was observed without alternations in diastolic [Ca]SR. Additionally, alternating cells were observed, in which diastolic [Ca]SR fluctuations occurred interspersed by depletions in which the amplitude was unrelated to the preceding diastolic [Ca]SR. In all forms of alternans, the SR Ca release rate was higher during large depletions than during small depletions. Although [Ca]SR exerts major influence on SR Ca release, alternations in [Ca]SR are not required for Ca 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 alternans. However, once such a weak SR Ca release occurs, it can result in increased [Ca]SR and further enhance SR Ca release at the next beat. In this way, diastolic [Ca]SR alternans can enhance frequency-induced Ca alternans, even if they initiate by other means.",
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