Mechanisms of Intrinsic Beating Variability in Cardiac Cell Cultures and Model Pacemaker Networks
Julien GC Ponard 1, Aleksandar A Kondratyev 1 and Jan P Kucera 1*
1 University of Bern
* To whom correspondence should be addressed. E-mail: kucera{at}pyl.unibe.ch.
Submitted on June 21, 2006
Revised on August 3, 2006
Accepted on 30 January 2007
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Abstract |
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Heart rate variability (HRV) exhibits fluctuations characterized by a power law behavior of its power spectrum. The interpretation of this nonlinear HRV behavior, resulting from interactions between extracardiac regulatory mechanisms, could be clinically useful. However, the involvement of intrinsic variations of pacemaker rate in HRV has scarcely been investigated.
We examined beating variability in spontaneously active incubating cultures of neonatal rat ventricular myocytes using microelectrode arrays. In networks of mathematical model pacemaker cells, we evaluated the variability induced by the stochastic gating of transmembrane currents, of calcium release channels and by the dynamic turnover of ion channels.
In the cultures, spontaneous activity originated from a mobile focus. Both the beat-to-beat movement of the focus and beat rate variability exhibited a power law behavior. In the model networks, stochastic fluctuations in transmembrane currents or stochastic gating of calcium release channels did not reproduce the spatiotemporal patterns observed in vitro. In contrast, long-term correlations produced by the turnover of ion channels induced variability patterns with a power law behavior similar to those observed experimentally.
Therefore, phenomena leading to long-term correlated variations in pacemaker cellular function may, in conjunction with extracardiac regulatory mechanisms, contribute to the nonlinear characteristics of HRV.
Key Words:
cardiac rhythm generation, cardiomyocyte cultures, heart rate variability, microelectrode arrays, nonlinear dynamics, sinoatrial node
