NDLI: Alternans of cardiac calcium cycling in a cluster of ryanodine receptors: a simulation study

Content Provider	PubMed Central
Author	Tao, T. O'neill, S. C. Diaz, M. E. Li, Y. T. Eisner, D. A. Zhang, H.
Abstract	Mechanical alternans in cardiac muscle is associated with intracellular Ca2+ alternans. Mechanisms underlying intracellular Ca2+ alternans are unclear. In previous experimental studies, we produced alternans of systolic Ca2+ under voltage clamp, either by partially inhibiting the Ca2+ release mechanism, or by applying small depolarizing pulses. In each case, alternans relied on propagating waves of Ca2+ release. The aim of this study is to investigate by computer modeling how alternans of systolic Ca2+ is produced. A mathematical model of a cardiac cell with 75 coupled elements is developed, with each element contains L-type Ca2+ current, a subspace into which Ca release takes place, a cytoplasmic space, sarcoplasmic reticulum (SR) release channels [ryanodine receptor (RyR)], and uptake sites (SERCA). Interelement coupling is via Ca2+ diffusion between neighboring subspaces via cytoplasmic spaces and network SR spaces. Small depolarizing pulses were simulated by step changes of cell membrane potential (20 mV) with random block of L-type channels. Partial inhibition of the release mechanism is mimicked by applying a reduction of RyR open probability in response to full stimulation by L-type channels. In both cases, systolic alternans follow, consistent with our experimental observations, being generated by propagating waves of Ca2+ release and sustained through alternation of SR Ca2+ content. This study provides novel and fundamental insights to understand mechanisms that may underlie intracellular Ca2+ alternans without the need for refractoriness of L-type Ca or RyR channels under rapid pacing.
Related Links	http://dx.doi.org/10.1152/ajpheart.01086.2007
Starting Page	598
File Format	PDF
ISSN	03636135
e-ISSN	15221539
Journal	American Journal of Physiology - Heart and Circulatory Physiology
Issue Number	2
Volume Number	295
Language	English
Publisher	American Physiological Society
Publisher Date	2008-06-01
Access Restriction	Open
Rights Holder	American Physiological Society
Subject Keyword	Physiology (medical) Physiology Cardiology and Cardiovascular Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Cardiology and Cardiovascular Medicine

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