Calcium instabilities in mammalian cardiomyocyte networks
Harold Bien 1, Lihong Yin 1 and Emilia Entcheva 1*
1 Stony Brook University
* To whom correspondence should be addressed. E-mail: emilia.entcheva{at}sunysb.edu.
Submitted on March 22, 2005
Revised on May 19, 2005
Accepted on 15 December 2005
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Abstract |
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The degeneration of a regular heart rhythm into fibrillation (a chaotic or chaos-like sequence) can proceed via several classical routes described by nonlinear dynamics: period-doubling, quasiperiodicity or intermittency. In this study we experimentally examine one aspect of cardiac excitation dynamics - the long-term evolution of intracellular calcium signals in cultured cardiomyocyte networks subjected to increasingly faster pacing rates via field stimulation. In this spatially-extended system, we observed alternans and higher order periodicities, extra beats, and skipped beats or blocks. Calcium instabilities evolved non-monotonically with prevalence of phase locking or Wenckebach rhythm, low-frequency magnitude modulations (signature of quasiperiodicity), and switches between patterns with occasional bursts (signature of intermittency), but period-doubling bifurcations were rare. Six ventricular fibrillation (VF)-resembling episodes were pace-induced, for which significantly higher complexity was confirmed by approximate entropy (ApEn) calculations. The progressive destabilization of the heart rhythm by co-existent frequencies, seen in this study, can be related to theoretically predicted competition of control variables (voltage and calcium) at the single cell level, or to competition of excitation and recovery at the cell network level. Optical maps of the response revealed multiple local spatiotemporal patterns, and the emergence of longer-period global rhythms as a result of wavebreak-induced reentries.
Key Words:
alternans, cultured cells, fibrillation, intracellular calcium, optical mapping, quasiperiodicity
