Mechanisms of intrinsic beating variability in cardiac cell cultures and model pacemaker networks

Ponard, Julien G C; Kondratyev, Aleksandar A; Kucera, Jan P (2007). Mechanisms of intrinsic beating variability in cardiac cell cultures and model pacemaker networks. Biophysical journal, 92(10), pp. 3734-52. Bethesda, Md.: Biophysical Society 10.1529/biophysj.106.091892

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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 and 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 and 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology
UniBE Contributor:	Kondratyev, Aleksandar, Kucera, Jan
ISSN:	0006-3495
ISBN:	17325022
Publisher:	Biophysical Society
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:53
Last Modified:	05 Dec 2022 14:16
Publisher DOI:	10.1529/biophysj.106.091892
PubMed ID:	17325022
Web of Science ID:	000245852600037
URI:	https://boris.unibe.ch/id/eprint/22288 (FactScience: 33896)