Evolution of Cardiac Calcium Waves from Stochastic Calcium Sparks

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ID: 118648
2001
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Abstract
We present a model that provides a unified framework for studying Ca2+ sparks and Ca2+ waves in cardiac cells. The model is novel in combining 1) use of large currents (approximately 20 pA) through the Ca2+ release units (CRUs) of the sarcoplasmic reticulum (SR); 2) stochastic Ca2+ release (or firing) of CRUs; 3) discrete, asymmetric distribution of CRUs along the longitudinal (separation distance of 2 microm) and transverse (separated by 0.4-0.8 microm) directions of the cell; and 4) anisotropic diffusion of Ca2+ and fluorescent indicator to study the evolution of Ca2+ waves from Ca2+ sparks. The model mimics the important features of Ca2+ sparks and Ca2+ waves in terms of the spontaneous spark rate, the Ca2+ wave velocity, and the pattern of wave propagation. Importantly, these features are reproduced when using experimentally measured values for the CRU Ca2+ sensitivity (approximately 15 microM). Stochastic control of CRU firing is important because it imposes constraints on the Ca2+ sensitivity of the CRU. Even with moderate (approximately 5 microM) Ca2+ sensitivity the very high spontaneous spark rate triggers numerous Ca2+ waves. In contrast, a single Ca2+ wave with arbitrarily large velocity can exist in a deterministic model when the CRU Ca2+ sensitivity is sufficiently high. The combination of low CRU Ca2+ sensitivity (approximately 15 microM), high cytosolic Ca2+ buffering capacity, and the spatial separation of CRUs help control the inherent instability of SR Ca2+ release. This allows Ca2+ waves to form and propagate given a sufficiently large initiation region, but prevents a single spark or a small group of sparks from triggering a wave.
Reference Key
balke2001biophysicalevolution Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Leighton T. Izu,W. Gil Wier,C. William Balke;Leighton T. Izu;W. Gil Wier;C. William Balke;
Journal Biophysical journal
Year 2001
DOI
10.1016/s0006-3495(01)75998-x
URL
https://sciprofiles.com/publication/view/7a26ad37fb4b40242103b8c9d43069e8
Keywords
model evolution stochastic release ca2 sparks waves cru microm National Center for Biotechnology Information NCBI NLM MEDLINE animals pubmed abstract nih national institutes of health national library of medicine models research support u.s. gov't P.H.S. linear models in vitro techniques kinetics stochastic processes myocardium / cytology buffers Biophysics biophysical phenomena pmid:11159386 pmc1301217 doi:10.1016/s0006-3495(01)75998-x l t izu w g wier c w balke calcium signaling / physiology* cardiovascular* myocardium / metabolism* nonlinear dynamics sarcoplasmic reticulum / metabolism

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