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 language||English (US)|
|Number of pages||9|
|State||Published - Oct 2006|
- Excitation/contraction coupling
- Sarcoplasmic reticulum
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine